WO2026015019A1 - Biodegradable thermoplastic polyoxazoline based copolymers - Google Patents

Abstract

The invention is directed to a biodegradable, thermoplastic multiblock copolymer, to a process for preparing a biodegradable, thermoplastic multiblock copolymer, to the use of a biodegradable thermoplastic multiblock copolymer, to a composition for the delivery of at least one pharmacologically active compound to a host, and a medical device comprising a biodegradable, thermoplastic multiblock copolymer. The biodegradable, thermoplastic multiblock copolymers of the invention comprise at least one prepolymer (A) segment and at least one hydrolysable amorphous prepolymer (B) segment, wherein the segments are linked by a multifunctional chain extender, wherein the at least one prepolymer (A) segment comprises: a) one or more hydrolysable linkages, b) a water-soluble polyoxazoline-based polymer, and c) reaction products of one or more cyclic monomers and/or one or more non-cyclic monomers, wherein the water-soluble polyoxazoline-based polymer is a polymer containing a repeating unit of structure −[N(COR¹)CH₂CH₂]_n− where R¹ is independently selected for each repeating unit from an alkyl group and n is 3-100, and wherein the multiblock copolymer is amorphous.

Description

P137041PC00 Title: BIODEGRADABLE THERMOPLASTIC POLYOXAZOLINE BASED COPOLYMERS BACKGROUND OF THE INVENTION The invention is directed to a biodegradable, thermoplastic polyoxazoline based copolymer, to a process for preparing a biodegradable, thermoplastic polyoxazoline based copolymer, to the use of a biodegradable thermoplastic polyoxazoline copolymer, to a pharmaceutical composition for the delivery of at least one pharmacologically active compound to a host. Biodegradable polymers have received increased attention over the past decade for use in long-acting injectable dosage forms, either systemic or site-specific drug delivery. Biodegradable long-acting injectable dosage forms can significantly improve the pharmacokinetics of therapeutic compounds. This is especially relevant in the treatment of chronic diseases and for compounds with a narrow therapeutic window since systemic plasma concentrations can be reduced with a concurrent reduction in undesirable side effects. Additionally, many new pharmacologically active compounds have short half-lives, necessitating frequent injection to achieve therapeutically effective plasma levels. Patient convenience, therapy compliance and the high costs associated with frequent dosing regimens for parenterally administered pharmacologically active compounds have increased the interest in biodegradable sustained-release dosage forms. Poly(D,L-lactic acid) (PLA) and copolymers of lactic acid and glycolic acid (PLGA), are the most widely applied biodegradable polymers for use in parenteral sustained release depot formulations. These polymers have the advantage that they have a proven track record of clinical use, are generally considered highly biocompatible and degrade into non-toxic degradation products that are metabolised and/or excreted from the body via known pathways. As a result, PLGA, and PLAA have been adopted and successfully used for the development of long-acting injectable and implantable depot formulations for small molecules, such as risperidone (Risperdal^® Consta), dexamethasone (Ozurdex^®) and triamcinolone acetonide (Zilretta^®), and therapeutic peptides such as leuprolide (Lupron^® Depot), goserelin (Zoladex^®) and octreotide (Sandostatin^® LAR). However, PL(G)A polyesters exhibit certain physicochemical and degradation characteristics that limit their use and make them less suitable as release controlling excipient in long-acting formulations for peptides and biological moieties, such as recombinant proteins, monoclonal antibodies, antibody fragments, oligonucleotides and nucleic acids. Firstly, PL(G)A (co)polyesters are relatively hydrophobic and as a result, do not provide an optimal environment for hydrophilic or amphiphilic polypeptides. Polypeptides may adsorb to the polymer, resulting in the slow and incomplete release, structural unfolding and/or aggregation. Secondly, the ability to manipulate the release of encapsulated polypeptides, and especially larger polypeptides such as (recombinant) proteins, growth factors or (monoclonal) antibodies, is limited since diffusion of such polypeptides through the relatively rigid, hydrophobic and non-swellable PL(G)A matrices is negligible. The release of polypeptides from PL(G)A copolymers, therefore, depends on diffusion via pores present in the matrix and on the degradation of the polymer matrix. Typically, the encapsulated polypeptide remains entrapped in the PL(G)A matrix until the moment the latter has degraded to such an extent that it loses its integrity or dissolves, resulting in biphasic or triphasic degradation-dependent release, typically observed for PL(G)A-based extended release polypeptide formulations. Finally, during the degradation of PL(G)A copolymers, acidic moieties are formed that accumulate in the rigid and non-swellable PL(G)A matrix resulting in the formation of an acidic micro-environment in the polymer matrix with in situ pHs that can be as low as 1-2. Such acidic conditions may have a deleterious effect on the structural integrity and biological activity of the encapsulated polypeptide, potentially leading to reduced therapeutic efficacy or side effects. The encapsulated polypeptides may form aggregates leading to incomplete release and enhanced immunogenicity. Moreover, the polypeptide may be chemically modified. Peptide acylation and adduct formation have been reported for PL(G)A-based extended-release polypeptide formulations such as Sandostatin^® LAR extended-release octreotide microparticles (Ghassemi et al., Pharm. Res. 2012, 29(1), 110-20). The limitations of PL(G)A-based amorphous polymers regarding the delivery of polypeptides can be resolved by using biodegradable polyester-based polymers containing a hydrophilic water-swellable polymer moiety in their structure. WO-A-2005/068533 describes amorphous polyether ester multiblock copolymers containing water-soluble polyethylene glycol (PEG) units. Due to their low glass transition temperature (Tg) of < 37 °C under physiological conditions, these amorphous multiblock copolymers are permeable for both low molecular weight polypeptides such as leuprolide as well as for the acidic degradation products formed upon hydrolysis of the polymer. As a consequence, the gradual release of such polypeptides as well as the (acidic) degradation products that are being formed can be achieved – thereby preventing the accumulation of acidic degradation products in the polymer matrix and the formation of an acidic microenvironment. Despite their usefulness for sustained release of small molecule drugs and low molecular weight peptides, the amorphous multiblock copolymers disclosed in WO-A-2005/068533 are not suitable for the sustained release of larger polypeptides such as recombinant proteins and monoclonal antibodies. This is due to the fact that high weight fractions of water soluble PEG would need to be introduced into such amorphous multiblock copolymers as to create a polymer matrix with sufficient swelling degree to allow diffusion-controlled release of the encapsulated large polypeptide. However, the incorporation of large weight fractions of PEG in the structure of such an amorphous multiblock copolymer dramatically reduces its Tg to values below room temperature or even below 0 °C. Amorphous multiblock copolymers with such a low T_g typically suffer from processability issues (sticky polymers) and cannot be processed into solid drug delivery formulations, such as microspheres or implants. Furthermore, there is a high chance that extended release drug delivery products derived from such low T_g amorphous multiblock copolymers will suffer from stability issues and have insufficient shelf life when stored under ambient or refrigerated conditions. To overcome the shortcomings encountered with the amorphous multiblock copolymers disclosed in WO-A-2005/068533, the inventors developed biodegradable phase-separated thermoplastic segmented multiblock copolymers based on a crystalline poly(^-caprolactone) block (as disclosed in WO-A-2012/005594) or a crystalline poly(L-lactide) block (as disclosed in WO-A-2013/015685) in combination with a PEG containing hydrophilic block. Such multiblock copolymers allow the preparation of depot formulations with long-term sustained release of structurally intact and biologically active polypeptides over extended periods of time. Hydrophilic phase separated segmented multiblock copolymers containing a hydrophobic poly(^-caprolactone)-based crystalline block, as disclosed in WO-A-2012/005594, were found to be well processable into implants by hot melt extrusion and allowed the long-term sustained release of peptides and proteins (Stankovic et al., Eur. J. Pharm. Sci.2013, 49(4), 578-587). Hydrophilic phase-separated segmented multiblock copolymers containing a hydrophobic poly(L-lactide)-based crystalline block, as disclosed in WO-A-2013/015685, were shown to have highly beneficial attributes in regard to protein delivery. Especially multiblock copolymers composed of a poly(^-caprolactone)-PEG-poly(^-caprolactone)-based hydrophilic block in combination with a poly(L-lactide)-based crystalline block (PCL multiblock copolymers) were found to exhibit promising characteristics allowing long-term sustained release of structurally intact biologics when formulated into microparticles (Int. J. Pharm.2017, 534(1-2), 229-236; J. Control Release 2018, 269, 258-265; ACS Omega 2019, 4(7), 11481-11492). The authors further found that the biodegradable, phase-separated, thermoplastic multiblock copolymers containing a poly(L-lactide) crystalline block have a degradation time of 3-4 years. Multiblock copolymers containing a poly(^-caprolactone) crystalline block are expected to have an even longer degradation time. For the majority of sustained-release drug delivery formulations, such a degradation time is unacceptably long, as it would lead to polymer accumulation upon repeated injection and could potentially induce long-term tolerability issues. It would be desirable to have multiblock copolymers with a degradation time of not more than two or three times the duration of drug release as to avoid accumulation of polymer in the body upon repeated injection. For long-acting dosage forms with a typical release duration of 3 to 6 months this would correspond with a degradation time of 6 to 18 months, depending on the duration of release. In addition, due to their high melting temperature (120-140 °C), most of the semicrystalline poly(L-lactide) -based multiblock copolymers disclosed in WO-A-2013/015685 require high temperatures for processing into implants via hot melt extrusion, injection moulding or 3D printing, which could lead to thermal-stress induced degradation of the incorporated drug. In addition, semicrystalline polymers demonstrate thermoplastic elastomer behaviour which makes them being able to recover their shape after being exposed to high stress. Even though highly beneficial for many applications, these polymers stand practically useless in applications like microneedles where easy penetration through skin and easy breakage are required. Finally, the hardening of microspheres prepared of semicrystalline poly(L-lactide)-based multiblock copolymers via solvent extraction/evaporation-based emulsification processes or spray-drying strongly depends on the crystallisation rate of the semicrystalline block. Multiple factors such as polymer concentration, rate of solvent removal, type of active pharmaceutical ingredient or temperature, strongly affect the crystallisation rate of the polymer during microsphere production, and thus small changes in those parameters can drastically impact the hardening of the microspheres. As a consequence, the production of microspheres using such polymers is accompanied with challenges regarding reproducibility, scaling up and storage stability. At the same time, it would be beneficial to retain the excellent tunability of the drug release kinetics reported for poly(L-lactide) and poly(^-caprolactone)-based multiblock copolymers disclosed in WO-A-2013/015685 and WO-A-2012/005594. The above-mentioned drawbacks regarding the use of semicrystalline polymers can be overcame by using rigid amorphous polymers for preparation of long-acting injectable formulations. However, as described above, the typical amorphous biodegradable polyesters, including the amorphous multiblock copolymers disclosed in WO-A-2005/068533, that allow sustained release of polypeptides do not have the required thermomechanical characteristics to obtain solid and stable long-acting injectable formulations. WO-A-2011/002285 describes a drug delivery system comprising a solid dispersion of bioactive compound in water soluble matrix containing at least 50 % polyoxazoline (POz). Vervaet et al. (Materials Today Bio 2022, 16, 100414) demonstrated use of polyoxazolines as a versatile platform to adjust the release rate of API from prepared tablets and enable sustained release even at 70 wt.% loading. Changing the alkyl group on the polymer side-chain in a form of copolymer controlled polymer solubility in water and impacted the release rate of API in aqueous medium. CN-A-102731791 discloses a biodegradable block copolymer with temperature-sensitive properties. The block copolymer is a BAB or ABA type triblock copolymer composed of polyester block A and poly(2-alkyl-2-oxazoline) block B. US-A-2006/0182710 describes a biodegradable POz-based amphiphilic triblock copolymer and a pharmaceutical formulation comprising the same. The amphiphilic triblock copolymer comprises a poly(lactide) as a hydrophobic block and a polyoxazoline as a hydrophilic block. Triblock copolymers described in patent are used for the preparation of micellar pharmaceutical formulations with high encapsulation up to 60 wt.% of active. Besides the mentioned amorphous triblock copolymer based on POz, semicrystalline segmented and alternating PCL−b−POz multiblock copolymers have been prepared and studied for their resistance against protein adsorption and their ability for 3D printing (RSC Adv. 2016, 6, 69930 and Eur. Polym. J.2021, 151, 110449). CN-A-108926531 discloses an amphiphilic polyurethane, wherein the hydrophobic segment is a polyurethane containing a reduction-sensitive disulphide bond, and the hydrophilic segment is a pH-responsive polyoxazoline. Bueno et al. (Eur. Polym. J.2021, 151, 1104449) disclose the preparation of segmented polyurethanes based on poly(^-caprolactone) and poly(2-ethyl-2-oxazoline) diols and 1,6-hexamethylene diisocyanate. The two prepolymer diols are first converted into corresponding diisocyanates using 1,6-hexamethylene diisocyanate and then the prepolymers with diisocyanate end groups are chain extended using butanediol as chain extender. SUMMARY OF THE INVENTION Objective of the invention is to overcome one or more drawbacks observed in the prior art. In a first aspect, the invention is directed to a biodegradable, thermoplastic multiblock copolymer, comprising at least one prepolymer (A) segment and at least one hydrolysable amorphous prepolymer (B) segment, wherein the segments are linked by a multifunctional chain extender, wherein the at least one prepolymer (A) segment comprises: a) one or more hydrolysable linkages, b) a water soluble polyoxazoline-based polymer, and c) reaction products of one or more cyclic monomers and/or one or more non-cyclic monomers, wherein the water-soluble polyoxazoline-based polymer is a polymer containing a repeating unit of structure –[N(COR¹)CH2CH2]n−, wherein R¹ is independently selected for each repeating unit from an alkyl group and n is 3-100, and wherein the multiblock copolymer is amorphous. In a further aspect, the invention is directed to a biodegradable, thermoplastic multiblock copolymer, comprising at least one prepolymer (A) segment and at least one hydrolysable amorphous prepolymer (B) segment, wherein the segments are linked by a multifunctional chain extender, wherein (i) the at least one prepolymer (A) segment comprises a water-soluble polyoxazoline-based polymer, wherein the water-soluble polyoxazoline-based polymer is a polymer containing a repeating unit of structure −[N(COR¹)CH₂CH₂]_n− where R¹ is independently selected for each repeating unit from an alkyl group and n is 3-100, and (ii) the at least one hydrolysable amorphous prepolymer (B) segment comprises the , wherein n is 4-100, such as 5-50; x is 0.25-1 and x + y = 1; p is 0 or 1; R¹ and R² are independently selected from hydrogen and C₁-C₄ alkyl; wherein r is 1-100, s is 1-12, t is 1-10, R³ is selected from hydrogen and C1-C6 alkyl, R⁴ is selected from hydrogen and C1-C4 alkyl, and v is 1-100, w is 1-12, and R⁶ is selected from hydrogen and C1-C6 alkyl. I_{n a yet further aspect, the invention is directed to a process for preparing a} biodegradable, thermoplastic multiblock copolymer according to the invention, comprising a chain-extension reaction of prepolymer (A) and prepolymer (B) in the presence of a multifunctional chain extender. In yet a further aspect, the invention is directed to a composition for delivery of at least one pharmacologically active compound to a host, comprising at least one pharmacologically active compound encapsulated in a matrix, wherein said matrix comprises at least one biodegradable, thermoplastic multiblock copolymer according to the invention. In yet a further aspect, the invention is directed to a medical device in the form of microspheres, microparticles, nanoparticles, nanospheres, rods, solid implants, gels, in situ forming implants, coatings, films, sheets, sprays, tubes, membranes, meshes, fibres, scaffolds or plugs, wherein said medical device comprises a biodegradable, thermoplastic multiblock copolymer of the invention. BRIEF DESCRIPTION OF THE DRAWINGS Fig.1 In vitro degradation of POz-based copolymers and comparison to PEG-based multiblock copolymer Fig.2 SEM micrographs of POz-based copolymer microspheres demonstrating degradation of microspheres over time Fig.3 Cumulative in vitro release of ropivacaine from microspheres made using 20LP10L20-GLL40 (15 / 85) Fig.4 SEM micrographs of ropivacaine loaded MSP based on POz-based copolymers Fig.5 Cumulative in vitro release of ropivacaine from microspheres prepared of 20LP10L20-GLL40, 20LPOz10L20-L40 and 20LPOz10L20-GLL40 Fig.6 Cumulative in vitro release of ropivacaine from microspheres prepared of 10LPOz10L20-L40, 20LPOz10L20-L40, 30LPOz10L20-L40 and 40LPOz10L30-L40 Fig.7 SEM micrographs of LNG loaded implants prepared using hot melt extrusion. Fig.8 Cumulative in vitro release of LNG from POz-based copolymers Fig.9 Cumulative in vitro release of LNG from LNG implants: comparison between POz- and PEG-based copolymers and PDLG 5004 Fig.10 Levonorgestrel serum concentration in rats following subcutaneous injection of LNG implants composed of 40LPOZ10L30-GLL40 (G / LL = 15 / 85) and 20LP10L20-GLL40 (G / LL = 25 / 75) and PLGA DLG50-5E Fig.11 The change in shape over time of LNG loaded implants made of 60LPOZ10L30-GLL40 and PDLG 5004 Fig.12 In vitro release comparison between POz-based copolymers and PLGA Fig.13 In vitro release comparison between POz and PEG-based copolymers Fig.14 Cumulative in vitro release of ropivacaine from in situ forming implants prepared of 10LPOz6L12-L20, 20LPOz6L12-L20, 10CPOz6C12-L20, 20CPOz6C12-L20 Fig.15 IVR comparison between POz-based copolymers and Eligard 3M Fig.16 The effect of polymer concentration of 10CPOz6C12-L20 on the release profile of leuprolide acetate. Fig.17 SEM micrographs of BSA loaded MSPs prepared using POz copolymers Fig.18 Cumulative BSA release from xxLPOz10L20-L40 polymers Fig.19 Cumulative release of BSA from xxLPOz10L30-L40 and xxLPOz20L50-L40 polymers Fig.20 SEM micrographs of IgG-MSPs based on POz copolymers Fig.21 Cumulative IVR release of IgG from POz based MSPs Fig.22 The effect IgG loading on the cumulative release from 30LPOz20L50-L40-based MSP DETAILED DESCRIPTION OF THE INVENTION The term “prepolymer” as used herein is meant to refer to the polymer segments that are linked by a multifunctional chain extender, together making up the multiblock copolymer of the invention. Each prepolymer may be obtained by polymerisation of suitable monomers, which monomers thus are the chemical units of each prepolymer. The properties of the prepolymers and, by consequence, of the multiblock copolymer of the invention, can be controlled, amongst others, by choosing a prepolymer of a suitable composition and molecular weight. The terms “block” and “segment” as used herein are meant to refer to distinct regions in a multiblock copolymer. The terms block and segment are used interchangeably. The term “pendant” as used herein is meant to refer to the short linear polymer chain segment(s) that hangs off the backbone of the main chain or the (prepolymer) multiblock copolymer. The term “multiblock” as used herein is meant to refer to the presence of at least two distinct prepolymer segments in a polymer chain. As commonly known, a multiblock copolymer comprises a plurality of polymer blocks of at least the two chemically distinct prepolymer segments, wherein the copolymer includes more than three blocks, wherein the blocks may be in a regular or irregular repeating sequence. A prepolymer in such a multiblock can have a functional moiety, such as a POZ chain, as a pendent or linear part of the chain. The term “thermoplastic” as used herein is meant to refer to the non-crosslinked nature of the multiblock copolymer. Upon heating, a thermoplastic polymer becomes fluid, whereas it solidifies upon (re-)cooling. Thermoplastic polymers are soluble in proper solvents. The term “hydrolysable” as used herein is meant to refer to the ability to react with water upon which the molecule is cleaved. Hydrolysable segments, for instance, include esters, orthoesters, carbonates, anhydrides, amides, phosphates, phosphazenes, urethanes, and ureas. Under physiological conditions, only ester, orthoester, carbonate and phosphazene groups react with water in a reasonable time scale. The term “multifunctional chain extender” as used herein is meant to refer to the presence of at least two reactive groups on the chain extender that allow chemically linking reactive prepolymers thereby forming a multiblock copolymer. The term “water-soluble polymer’’ as used herein is meant to refer to a polymer that has good solubility in an aqueous medium, such as water, under physiological conditions. This polymer, when copolymerised with more hydrophobic moieties, renders the resulting copolymer swellable in water. The water-soluble polymer can be a diol, a diamine or a diacid. The diol or diacid is suitably used to initiate the ring-opening polymerisation of cyclic monomers. Analogously, a polymer insoluble in water is meant to refer to a polymer that has poor solubility in an aqueous medium, such as water. Preferably, a polymer insoluble in water has a solubility in distilled water of 0.5 wt.% or less at 25 °C, more preferably 0.1 wt.% or less. The term “swellable” as used herein is meant to refer to the uptake of water by the polymer. The swelling ratio can be calculated by dividing the mass of the water-swollen copolymer by that of the dry copolymer. The term “pharmacologically active compound” as used herein is intended to be broadly interpreted as any agent that provides a therapeutic or prophylactic effect. Such agents include, but are not limited to, antimicrobial agents (including antibacterial and antifungal agents), anti-viral agents, anti-tumour agents, hormones and immunogenic agents. The term “pharmacologically active compound” as used herein is meant to refer to a compound that is pharmacologically active in a mammalian body, more in particular in the human body. A redesign of multiblock copolymers was conducted in an attempt to obtain fully (or completely) amorphous polymers with improved thermomechanical characteristics that have reduced erosion time to avoid polymer accumulation upon repeated administration and improve the long-term local tolerability. It is a prerequisite that the fully amorphous copolymer should have a sufficiently high T_g to be processed into solid drug delivery formulations that are stable under ambient storage conditions. The amorphous multiblock copolymers in WO-A-2005/068533 contain relatively large amounts of ^-caprolactone or polyethylene glycol (PEG) in the prepolymer (A) segment resulting in relatively low Tg values varying from -24 °C to 21.4 °C, which is typically too low to obtain drug products with sufficient shelf life under ambient or refrigerated storage conditions. To obtain hydrophilic polymers with sufficient swelling degree to allow diffusion-controlled extended release of small molecules with a molecular weight of about 1000 g/mol or less, polypeptides or polynucleotides with a molecular weight of about 1000 to about 5000 g/mol, and polypeptides or oligonucleotides with a molecular weight of about 5000 g/mol or more in combination with thermomechanical characteristics that allow good processability and sufficient storage stability, the low Tg PEG segments in prepolymer (A) segments of amorphous multiblock copolymers as disclosed in WO-A-2005/068533 should be replaced with alternative hydrophilic segment whose introduction into the prepolymer (A) segments would result into multiblock copolymers with the desired properties. The biodegradable multiblock copolymers of the invention are advantageous for controlled release of small molecules having a molecular weight of about 1000 g/mol or less. This is because their release can be controlled by adjusting the swelling and polymer degradation properties of the multiblock copolymers. In addition, the acceptable degradation (and related acceptable polymer life time / release duration balance) avoids accumulation of the polymer upon repeated administration which is observed for very slowly degrading crystalline polymers. Furthermore, the amorphous multiblock copolymers of the invention have a relatively high glass transition temperature, which ensures good product stability during storage. This combination of advantageous properties is neither obtained with amorphous PEG based multiblock copolymers as disclosed in WO-A-2005/068533 (too low glass transition temperature and consequently instable under ambient or refrigerated storage conditions), nor with PEG based semicrystalline multiblock copolymers as disclosed in WO-A-2013/015685 (crystalline L-lactide prepolymer (B) segment) and WO-A-2012/005594, which suffer from too slow degradation. The hydrophilic polymer segment used according to the invention comprises a polyoxazoline polymer (POz). POz has been reported to be nontoxic and is an emerging new class of water-soluble polymers used as a non-immunogenic alternative for PEG-based polymers in drug delivery field (Mero et al., Journal of Controlled Release 2008, 125, 87-95; Adams et al., Advanced Drug Delivery Reviews 2007, 59, 1504-1520). POz-based polymers showed no adverse effects in animal models and rapid renal clearance was observed without any significant accumulation in tissues (Tacey et al., Bioconjugate Chem.2011, 22, 976-986). POz-based polymers can be used as an alternative for PEG as a hydrophilic moiety in multiblock copolymers and can be present in the prepolymer segment (A) of multiblock copolymers as a pendant or linear segment that replaces linear PEG segments. POz polymers are typically prepared by reaction of an appropriate stoichiometric amount of 2-alkyl-2-oxazoline with an electrophilic initiator, followed by termination with a nucleophile such as a hydroxyl, thiol or amine. Similar to PEG, POz-based polymers are water soluble, do not undergo metabolism in the body and are excreted unchanged. One of the main advantage of POz over PEG is the possibility of preparing hydrophilic water-swellable polymers with significantly higher T_g as compared to PEG-containing polymers. Next to the biocompatibility and higher Tg, POz polymers are advantageous in terms of i) the ability to tightly control POz molecular weight/chain length ii) and the fact that the chemistry of POz allows the introduction of a variety of reactive or non-reactive side groups. In most examples of POz use for drug delivery they were applied as oral and transmucosal drug delivery systems in a form of powder, tablet, capsule or mucoadhesive sheet. The invention is directed to biodegradable, thermoplastic multiblock copolymers, comprising at least one prepolymer segment (A) segment and at least one hydrolysable amorphous prepolymer (B) segment, wherein the segments are linked by a multifunctional chain extender, wherein the at least one prepolymer (A) segment comprises: a) one or more hydrolysable linkages, b) a water soluble polyoxazoline-based polymer, and c) reaction products of one or more cyclic monomers and/or one or more non-cyclic monomers, wherein the water-soluble polyoxazoline-based polymer is a polymer containing a repeating unit of structure −[N(COR¹)CH₂CH₂]_n−, wherein R¹ is independently selected for each repeating unit from an alkyl group and n is 3-100, and wherein the multiblock copolymers are completely amorphous. The polyoxazoline-based polymer may be present as a pendant or linear chain. The multiblock copolymers of this invention are amorphous. The multifunctional chain extender is preferably an aliphatic chain extender. Contrary to other hydrophilic biodegradable polyesters such as PEG-PLGA diblock copolymers, PLGA-PEG-PLGA or PEG-PLGA-PEG triblock copolymers or amorphous PEG-containing multiblock copolymers as disclosed in WO-A-2005/068533, the multiblock copolymers of the invention have significantly higher glass transition temperatures regardless of the content of hydrophilic block. This allows the development of polypeptide releasing dosage forms that are highly stable under ambient storage conditions. Surprisingly, microspheres prepared of multiblock copolymers with a high content of POz-based polymer demonstrated good redispersion ability in aqueous medium, and no aggregation of microspheres was observed. Furthermore, the polymers of the invention demonstrated, unexpectedly, lower initial burst of the released drug both from microspheres and in situ forming implants, as compared to PEG containing analogues and PLGA polymers. Polymers of the invention exhibit outstandingly high encapsulation efficiency of antibodies inside of microspheres prepared using W/O/W emulsification solvent evaporation based microencapsulation process. Even more striking is the fact that the antibody encapsulated at such high loadings was released in sustained manner without high initial burst release. When compared to prior art semicrystalline polymers, the polymers of the invention degrade faster and their degradation kinetics can be easily tuned by changing the composition of the prepolymer segments used in combination with the polyoxazoline-based polymer containing prepolymer (A) segment in the multiblock copolymer. Moreover, preferably the multiblock copolymers of the invention are composed of an amorphous polyoxazoline-based polymer containing prepolymer (A) segment in combination with an amorphous poly(ester) prepolymer (B) segment. As a result, polymer crystallisation-related processability, reproducibility and storage stability problems, that are typically encountered for (semi)crystalline multiblock copolymers can be avoided. The multiblock copolymers of the invention surprisingly have desirable properties which render them suitable for sustained release of pharmacologically active compounds such as small molecules, peptides, proteins, (monoclonal) antibodies, antibody fragments, nucleic acids or oligonucleotides, such as an antisense oligonucleotides. The polyoxazoline-based polymers in the prepolymer segment (A) ensure that the multiblock copolymer swells in water, due to its water solubility, which allows the pharmacologically active compounds to be released from the polymer matrix via diffusion through these hydrophilic swollen domains. Next to that, as both the prepolymer (A) segment and the prepolymer (B) segment have a relatively high T_g, a multiblock copolymer composed of such high Tg prepolymer (A) segment and high Tg prepolymer (B) segment also has a relatively high Tg. Any drug product composed of such a high Tg multiblock copolymer would have better storage stability due to minimal polymer chain mobility resulting from the relatively high Tg. The prepolymer (A) segment comprises a water-soluble polyoxazoline-based polymer, and one or more hydrolysable linkages. Examples of hydrolysable linkages include esters linkages, orthoester linkages, carbonate linkages, anhydride linkages, amide linkages, phosphate linkages, phosphazene linkages, urethane linkages, and urea linkages. The prepolymer (A) segment comprises a water-soluble polyoxazoline-based polymer. This water-soluble polyoxazoline-based polymer refers to a polymer of 2-substituted-2-oxazoline containing a repeating unit of structure −[N(COR¹)CH₂CH₂]_n− where R¹ is independently selected for each repeating unit from an alkyl or cyclic alkyl group and n is from 3-100. The term “alkyl” refers to straight hydrocarbon groups comprising from one to ten carbon atoms such as methyl, ethyl, propyl, butyl and the like. The phrase also includes branched chain isomers of straight chain alkyl groups, including but not limited to: −CH(CH3)2, −CH(CH3) −(CH2CH3), −C(CH3)3, and others. The phrase also includes cyclic alkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and such rings substituted with straight and branched chain alkyl groups as defined above. The water-soluble polyoxazoline-based prepolymer (A) segment may also comprise blends with two or more of polyethers (such as polyethylene glycol (PEG), polytetramethylene oxide (PTMO), polypropylene glycol (PPG), and polytetramethylene ether glycol (PTMG), or one or more other water-soluble polymers (such as polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), polyvinyl caprolactam, poly(hydroxyethyl methacrylate) (poly-(HEMA)), or polyphosphazenes. Prepolymer (A) segment comprises a water-soluble polymer that is derived from polyoxazoline (POz). Preferably, POz can be water-soluble poly(2-ethyl-2-oxazoline), poly(2-methyl-2-oxazoline) and/or water-soluble copolymers of 2-ethyl-2-oxazoline or 2-methyl-2-oxazoline with more hydrophobic monomers such as 2-n-propyl-2-oxazoline, 2-n-propyl-2-oxazoline, 2-iso-propyl-2-oxazoline, 2-sec-butyl-2-oxazoline, 2-cyclopropyl-2-oxazoline. Most preferably, POz is poly(2-ethyl-2-oxazoline), Said polyoxazoline can, for example, have a number average molecular weight Mn of 400-10000 g/mol, preferably 500-5000 g/mol, more preferably 600-3000 g/mol. Typically, POz is prepared by ring opening polymerization of 2-alkyl-2-oxazoline, such as for example 2-ethyl-2-oxazoline, using an initiator. Examples of suitable initiators are methyl tosylate, ethyl tosylate, n-propyl tosylate, iso-propyl tosylate, n-butyl tosylate, iso-butyl tosylate, pentyl tosylate, hexyl tosylate, allyl tosylate, propargyl tosylate, 3-butynyl tosylate, methyl triflate, ethyl triflate, n-propyl triflate, iso-propyl triflate, n-butyl triflate, iso-butyl triflate, pentyl triflate, hexyl triflate, allyl triflate, propargyl triflate, 3-butynyl triflate, methyl nosylate, ethyl nosylate, n-propyl nosylate, iso-propyl nosylate, n-butyl nosylate, iso-butyl nosylate, pentyl nosylate, hexyl nosylate, allyl nosylate, propargyl nosylate, 3-butynyl nosylate, methyl iodide, benzyl bromide and trityl bromide. Quenching the reaction with an amine having two hydroxyl groups (like for example a diethanolamine) yields a linear POz having two OH-end groups at one end of the POz moiety, while the other end group originates from the initiator used in the preparation of the POz. Other suitable initiators are difunctional ethylene glycol bis(p-toluene sulphonate), diethylene glycol di(p-toluene sulphonate), triethylene glycol di(p-toluene sulphonate), ethylene glycol bistriflate, 1,4-dibenzyl bromide or trans-1,4-dibromo-2-butene. Quenching the reaction with the base (for example potassium hydroxide, sodium bicarbonate or tetramethylammonium hydroxide) yields a linear POz having one OH end group at both ends of the POz Prepolymer (A) comprises reaction products of one or more cyclic monomers and/or one or more non-cyclic monomers, preferably reaction products of one or more cyclic monomers. The presence of such reaction products in the prepolymer (A) segment, increases the overall degradation of the polymers due to degradable ester bonds next to the polyoxazoline block that results in a faster overall degradation of the multiblock copolymer. In particular, the presence of such reaction products can compensate for a relatively slower degradation rate that is generally seen for high Tg polymers. Cyclic monomers can, for instance, be selected from the group consisting of 2-substituted-2-oxazoline (such as 2-methyl-2-oxazoline or 2-ethyl-2-oxazoline), glycolide, L-lactide, D-lactide, D,L-lactide, ^-caprolactone, ^-valerolactone, trimethylene carbonate, tetramethylenecarbonate, 1,5-dioxepane-2-one, 1,4-dioxane-2-one (p-dioxanone), cyclic anhydrides (such as oxepane-2,7-dione), N-carboxyanhydrides of natural amino acids and their derivatives (such as N-carboxyalanine anhydride) and morpholine-2,5-diones based cyclic depsipeptides (such as 6-methyl-morpholine-2,5-dione). Non-cyclic monomers can, for instance, be selected from the group consisting of succinic acid, glutaric acid, adipic acid, sebacic acid, lactic acid, glycolic acid, hydroxybutyric acid, natural amino acids and their derivates (such as alanine), ethylene glycol, diethylene glycol, 1,4-butanediol, 1,6-hexanediol, 1,4-butanediamine and 1,6-hexanediamine. In case prepolymer (A) comprises segments containing polyoxazoline in combination with poly(D,L-lactide), the L / D ratio of the lactide may be away from unity (other than 50 / 50). For instance, an L / D ratio between 85 / 15 and 15 / 85 gives a completely amorphous homopolymer. Furthermore, it is known that an excess of one isomer (L or D) over the other increases the Tg of the poly(D,L-lactide). In case prepolymer (A) comprises segments containing polyoxazoline in combination with poly(D,L-lactide-co-glycolide), the D,L-lactide / glycolide molar ratio may be away from unity (other than 50 / 50). For instance, a D,L-lactide / glycolide molar ratio > 1 or < 1, such as would be the case for a poly(D,L-lactide-co-glycolide) with a D,L-lactide / glycolide molar ratio of 85 / 15 or 15 / 85, will lead to slower degradation as compared to poly(D,L-lactide-co-glycolide) with a D,L-lactide / glycolide molar ratio of 50 / 50. Furthermore, an excess of one monomer (D,L-lactide or glycolide) over the other increases the Tg of the poly(D,L-lactide-co-glycolide). Some non-limiting examples of suitable prepolymer (A) segments include, poly(D,L-lactide)-co-POz-co-poly(D,L-lactide), poly(glycolide)-co-POz-co-poly(glycolide), poly(ε-caprolactone)-co-POz-co-poly(ε-caprolactone), and poly(p-dioxanone)-co-POz-co-poly(p-dioxanone). It is also possible that prepolymer (A) segment does not have any hydrolysable linkages, but consists of polyoxazoline in combination with at least one hydrolysable , x is 0.25-1 and x + y = 1; p is 0 or 1; R¹ and R² are independently selected from hydrogen and C1-C4 alkyl; s is 1-12, t is 1-10, R³ is selected from hydrogen and C1-C6 alkyl, R⁴ is selected from hydrogen and C1-C4 alkyl, and R⁵ w is 1-12, and R⁶ is selected from hydrogen and C1-C6 alkyl. This provides for an alternative solution to the above disclosed multiblock copolymer with prepolymer (A) and (B) segments, wherein the prepolymer (A) segment comprises one or more hydrolysable linkages, reaction products of one or more cyclic monomers and/or one or more non-cyclic monomers, and a water soluble polyoxazoline based polymer. Suitably, also this alternative solution is amorphous. In this alternative, the reaction products of one or more cyclic monomers and/or one or more non-cyclic monomers may be absent in the prepolymer (A) segments. Preferably in this alternative case, R¹ and R² are independently C1-C4 alkyl, more preferably R¹ and R² are both CH3. More preferably, R¹ and R² are both CH3, x is 1 and Q¹ is 1,4-diethylcyclohexane. These polyorthoester prepolymer (B) segments can be synthesised by a polyaddition reaction between a diol and an acetal, more specifically from cyclohexane dimethanol (CHDM) and 3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5]undecane (_{DVTOSU) to obtain a CHDM based polyorthoester prepolymer (B). To obtain a bifunctional} diol-functionalised polyorthoester, an excess of CHDM over DVTOSU is preferably used and the polyaddition reaction can be monitored using NMR spectroscopy. Since polyorthoester based polymers are known to hydrolyse rapidly under acidic conditions, a mild base amine, such as triethyl amine, may be added to the reaction medium to prevent hydrolysis and decrease of the molecular weight of the polyorthoester. Such polyorthoester prepolymer (B) segments are disclosed, e.g., in WO-A-2023/177300, the complete contents of which are herewith incorporated by reference. The multiblock copolymers in WO-A-2023/177300, however, have a high weight fraction of a PEG-containing prepolymer (A) segment and accordingly a low Tg. The use of POz-based prepolymer (A) segments allows for creating amorphous multiblock copolymers with a high overall Tg. In addition, the prepolymer (A) segment can comprise a water-soluble polyoxazoline polymer and have, at one side or at each side of the water-soluble polyoxazoline polymer, any copolymer of the above-mentioned monomers. Some non-limiting examples of such prepolymer (A) segments include [poly(ε-caprolactone-co-D,L-lactide)]-co-POz-co-[poly(ε-caprolactone-co-D,L-lactide)], [poly(ε-caprolactone-co-glycolide)]-co-POz-co-[poly(ε-caprolactone-co-glycolide)], [poly(ε-caprolactone-co-p-dioxanone)]-co-POz-co-[poly(ε-caprolactone-co-p-dioxanone)], [poly(D,L-lactide-co-glycolide)]-co-POz-co-[poly(D,L-lactide-co-glycolide)], [poly(D,L-lactide-co-p-dioxanone)]-co-POz-co-[poly(D,L-lactide-co-p-dioxanone)], and [poly(glycolide-co-p-dioxanone)]-co-POz-co-[poly(glycolide-co-p-dioxanone)]. The prepolymer (A) segment comprises a water-soluble polymer. Typically, 5 % or more by total weight of the prepolymer (A) segment consists of water-soluble polyoxazoline polymer. Preferably 15 % or more by total weight of the prepolymer (A) segment consists of water-soluble polyoxazoline polymer, such as 20 % or more, 30 % or more, 40 % or more, 50 % or more, 60 % or more, or 70 % or more. Suitably, 95 % or less by total weight of prepolymer (A) consists of water-soluble polyoxazoline polymer, such as 90 % or less, 85 % or less. The prepolymer (A) segment can have a number average molecular weight (Mn) of 400 g/mol or more, such as 500 g/mol or more, such as 600 g/mol or more, 1000 g/mol or more, 1500 g/mol or more, or 2000 g/mol or more. Prepolymer (A) can have a M_n of 30000 g/mol or less, such as 20000 g/mol or less, 10000 g/mol or less, 8000 g/mol or less, 7000 g/mol or less, 5000 g/mol or less, 4000 g/mol or less, 3000 g/mol or less, or 2500 g/mol or less. The length of the prepolymers is preferably such that the resulting multiblock copolymer exhibits desired mechanical and thermal properties. Suitably, the prepolymer (A) segment can have a glass transition temperature of -50 °C or more, such as -40 °C or more, preferably -20 °C or more, more preferably 0 °C or more, most preferably 20 °C or more, such as 40 °C or more. The content of prepolymer (A) in the multiblock copolymer of the invention can be 1-99 % based on total weight of the multiblock copolymer, such as 5-95 %, 10-90 %, 20-80 %, 30-70 %, or 40-60 %. Preferably, the content of prepolymer (A) in the multiblock copolymer is in the range of 1-70 % based on total weight of the multiblock copolymer, such as 2-60 %, 3-50 %, 4-45 %, or 5-40 %. Prepolymer (A) may e.g. be prepared by ring-opening polymerisation. Thus, a prepolymer (A) may be a hydrolysable copolymer prepared by ring-opening polymerisation initiated by a polyoxazoline diol compound, in one embodiment having a random monomer distribution. The polyoxazoline diol compound can be an diol terminated aliphatic polyoxazoline chain with nitrogen of the initiating monomer unit is bound to a methyl group. The polyoxazoline diol compound can have molecular weight of 400-10000 g/mol. The prepolymer (A) synthesis by a ring-opening polymerisation is in one embodiment carried out in the presence of a catalyst. A suitable catalyst is Sn(Oct)2 with M / I = 5000-30000 (M / I is the monomer to initiator ratio). Prepolymer (A) may be a hydrolysable polyester, polyoxazoline ester, polyether ester, polycarbonate, polyester-carbonate, polyanhydride or copolymers thereof. The conditions for preparing such polymers are known in the art. For example, prepolymer (A) comprises reaction products of ester forming monomers selected from diols, dicarboxylic acids and hydroxycarboxylic acids. The hydrolysable prepolymer (A) segment suitably comprises a polymer according to Formula (I) or Formula (II) or a mixture thereof: −X−POz−X− (I) Y−POz−(X−)₂ (II), wherein, i_{) POz is the polyoxazoline-based polymer} ii) X are hydrolysable linkages, and iii) Y is an end group originating from the initiator used in the preparation of the polyoxazoline-based polymer. The end group originating from the initiator Y can suitably be a methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, pentyl, hexyl, allyl, propargyl, 3-butynyl, benzyl, trityl, dodecyl, hexadecyl, or octadecyl group. In one embodiment, Y is a methyl group. The hydrolysable amorphous prepolymer (B) segment is preferably a polyester, polyetherester, polyorthoester, polycarbonate or polyanhydride; or prepolymers of combined ester, orthoester, ether, anhydride and/or carbonate groups thereof, derived from cyclic monomers such as lactide (L,D or L/D), glycolide, ^-caprolactone, ^-valerolactone, trimethylene carbonate, tetramethylene carbonate, 1,5-dioxepane-2-one, 1,4-dioxane-2-one (p-dioxanone) or cyclic anhydrides (oxepane-2,7-dione). To fulfil the requirement of a high T_g, some of the above-mentioned monomers or combinations of monomers are more preferred than others. For example, prepolymer (B) containing the monomer lactide and/or glycolide are preferred or it can be combined with any of the other mentioned cyclic comonomers (^-caprolactone, ^-valerolactone, trimethylenecarbonate, 1,4-dioxane-2-one and combinations thereof). The prepolymer (B) segment is amorphous, contrary to (semi)crystalline prepolymers, such as poly(^-caprolactone) (PCL), that degrade relatively slowly. In accordance with the invention, the prepolymer (B) segment is based on hydrolysable amorphous prepolymer (B) segments to overcome drawbacks of slowly degrading multiblock copolymers with (semi)crystalline prepolymer (B) segments. A (semi)crystalline prepolymer (B) segment (such as PCL) would result in multiblock copolymers that degrade relatively slowly, thereby causing polymer accumulation upon repeated injection, and potential long-term tolerability issues. Preferably, the multiblock copolymers of the invention have a degradation time of not more than two or three times the duration of drug release to avoid accumulation of polymer in the body upon repeated injection. The amorphous prepolymer (B) segment is preferably selected from poly(D,L-lactide), poly(D,L-lactide-co-L-lactide), poly(D,L-lactide-co-glycolide), poly(L-lactide-co-glycolide), poly(ε-caprolactone-co-D,L-lactide), poly(ε-caprolactone-co-L-lactide), poly(ε-caprolactone-co-glycolide), poly(ε-caprolactone-co-p-dioxanone), poly(D,L-lactide-co-p-dioxanone), poly(L-lactide-co-p-dioxanone), poly(glycolide-co-p-dioxanone), or a polyorthoester derived from cyclohexane dimethanol and 3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5]undecane. The amorphous prepolymer (B) segment is most preferably selected from poly(D,L-lactide), poly(D,L-lactide-co-L-lactide), poly(D,L-lactide-co-glycolide), poly(L-lactide-co-glycolide), or a polyorthoester, derived from cyclohexane dimethanol and 3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5]undecane. The prepolymer (B) segment can have a number average molecular weight (Mn) of 1000 g/mol or more, such as 2000 g/mol or more, 2500 g/mol or more, or 3000 g/mol or more. Prepolymer (B) can have a Mn of 10000 g/mol or less, such as 9000 g/mol or less, or 8000 g/mol or less. The length of the prepolymers is preferably such that the resulting multiblock copolymer exhibits desired mechanical and thermal properties. The content of prepolymer (B) in the multiblock copolymer of the invention can be 1-99 % based on total weight of the multiblock copolymer, such as 5-95 %, 10-90 %, 20-80 %, 30-70 %, or 40-60 %. Preferably, the content of prepolymer (B) in the multiblock copolymer is in the range of 30-99 % based on total weight of the multiblock copolymer, such as 40-98 %, 50-97 %, 55-96 %, or 60-95 %. Advantageously, if the overall content of the prepolymer (B) segment in the multiblock copolymer is relatively higher than the content of the prepolymer (A) segment, the degradation characteristics of the resulting multiblock copolymer will predominantly be dictated by the prepolymer (B) segment. The prepolymer segments of the multiblock copolymer are linked by a multifunctional chain extender. This multifunctional chain extender is preferably a difunctional aliphatic chain extender. More preferably, the chain extender is a difunctional diisocyanate, such as 1,4-butane diisocyanate. Nonetheless, it is also possible to use a trifunctional (or higher functional) chain extender, such as a tri-isocyanate. At sufficiently low conversion, this will result in a branched multiblock copolymer. Branched copolymers may show improved creep characteristics. It is also possible to obtain branched multiblock copolymers by using a difunctional chain extender, when at least one of the prepolymers has more than two functional groups. The multiblock copolymers of the invention may have an intrinsic viscosity of 0.1 dl/g or more, preferably 0.1-3 dl/g, more preferably 0.2-2 dl/g, such as 0.3-1 dl/g. Intrinsic viscosity can, for instance, be measured at 25 °C in chloroform via a single point method using an Ubbelohde Viscosimeter (DIN), type 0C. Preferably, the multiblock copolymers of the invention are insoluble in water, i.e. insolubility in water is defined as having a solubility in distilled water of 0.5 wt.% or _{less at 25 °C, more preferably 0.1 wt.% or less.} In a further aspect, the invention is directed to a process for preparing a biodegradable, thermoplastic multiblock copolymer according to the invention, comprising a chain-extension reaction of prepolymer (A) and prepolymer (B) in the presence of a multifunctional chain extender. Such a process results in a multiblock copolymer wherein the prepolymers are randomly distributed throughout the multiblock copolymer. In this process, prepolymer (A), prepolymer (B) and the multifunctional chain extender may be as described herein. Segmented multiblock copolymers can be made by chain-extending a mixture of prepolymers, in the desired ratio, with an equivalent amount of a multifunctional chain extender, in one embodiment an aliphatic molecule, such as 1,4-butane diisocyanate (BDI), 1,6-hexamethylene diisocyanate, or another diisocyanate. The segmented copolymers may be made in solution. Suitably, the prepolymer(s) are dissolved in an inert organic solvent and the chain extender is added pure or in solution. In comparison to the preparation described by Bueno et al. (Eur. Polym. J.2021, 151, 1104449), the process of the invention advantageously has less synthesis steps. The low polymerisation temperature and short polymerisation time will prevent transesterification and the monomer distribution is the same as in the prepolymers that build the copolymer. On the contrary, longer reaction times may lead to transesterification reactions and to a more random (i.e. less blocky) monomer distribution. The materials obtained by chain-extending in the bulk can also be produced in situ in an extruder. The multiblock copolymers of the invention preferably exhibit at least one glass transition temperature Tg of 30 °C or more, preferably 40 °C or more, such as 40-110 °C. The multiblock copolymers may have more than one T_g, such as two or more T_gs. In an embodiment, the multiblock copolymers have two Tgs wherein a lower Tg is in the range of from -60 °C to 50 °C, such as from -30 °C to 30 °C, and a higher Tg is in the range of from 40 °C to 110 °C, such as from 50 °C to 100 °C. The multiblock segmented copolymers can be formed into formulations of various shape and dimensions using any known technique such as, for example, solvent extraction/evaporation-based emulsification processes, extrusion, (injection) moulding, solvent casting, spray-drying, spray-freeze drying, spray-congealing, electrospinning, or freeze drying. The latter technique is used to form porous materials. Porosity can be tuned by addition of co-solvents, non-solvents and/or leachables. Copolymers can be processed (either solid or porous) into microspheres, microparticles, microgranules, nanospheres, rods, films, sheets, sprays, tubes, membranes, meshes, fibres, plugs, coatings and other articles. Products can be either solid, hollow or (micro)porous. A wide range of biomedical implants can be manufactured for applications in for example wound care, skin recovery, nerve regeneration, vascular prostheses, drug delivery, meniscus reconstruction, tissue engineering, coating of surgical devices, ligament and tendon regeneration, dental and orthopaedic repair. The copolymers can be used alone or can be blended and/or co-extruded with other absorbable or non-absorbable polymers. In yet a further aspect, the invention is directed to a composition for the delivery of at least one pharmacologically active compound (e.g. a small molecule, peptide, protein, monoclonal antibody, antibody fragment, nucleic acid, or oligonucleotide, such as an antisense oligonucleotide) to a host, comprising the at least one pharmacologically active compound encapsulated in a matrix, wherein said matrix comprises at least one _{biodegradable, thermoplastic multiblock copolymer as defined herein. The amorphous} multiblock copolymers of the present invention allow for more reproducible and well scalable manufacturing of drug products, in contrast e.g. to manufacturing of drug products composed of semicrystalline multiblock copolymers due to their polymer crystallisation-dependent hardening. The composition may be in the form of one or more selected from the group consisting of microparticles, microspheres, microgranules,, nanoparticles, nanospheres, rods, solid implants, gels, in situ forming implants, coatings, films, sheets, sprays, tubes, membranes, meshes, fibres, plugs, and other configurations. For example, the composition may be in the form of microparticles, microspheres and/or microgranules. The average diameter of the microparticles, microspheres and/or microgranules is then preferably in the range of 0.1-1000 ^m, more preferably in the range of 1-100 ^m, even more preferably in the range of 10-70 ^m. The composition may also be in the form of an in situ forming implant, wherein the pharmacologically active compound is dissolved or suspended in a solution of the biodegradable, thermoplastic multiblock copolymer in an acceptable organic solvent such as n-methyl pyrrolidone (NMP), dimethyl sulphoxide (DMSO), benzyl benzoate (BB), benzyl alcohol, triacetin, glycofurol, low molecular weight polyethylene glycol, or combinations thereof. Following administration into the body, the solution may form in situ a depot by replacement of the organic solvent by aqueous body fluids, thereby entrapping the pharmacologically active compound in the biodegradable, thermoplastic multiblock copolymer depot. Subsequently, the pharmacologically active compound can be gradually released from the biodegradable, thermoplastic multiblock copolymer depot. The composition may also be in the form of a solid implant which can, for instance, be prepared by hot-melt extrusion or injection moulding. The pharmacologically active compound can be incorporated in the biodegradable, thermoplastic multiblock copolymer as a molecular blend or as a dispersion of solid particles. The at least one pharmacologically active compound in the pharmaceutical composition comprises, but is not limited to, a small molecule, having a molecular weight which in general is 1000 Da or less, a polypeptide, a polynucleotide, or combinations thereof. Polypeptides consist of amino acids linked by peptide bonds. Short polypeptides are also referred to as peptides, whereas longer polypeptides are typically referred to as proteins. One convention is that those polypeptide chains that are short enough to be made synthetically from the constituent amino acids are called peptides rather than proteins. However, with the advent of better synthetic techniques, polypeptides as long as hundreds of amino acids can be made, including full proteins like ubiquitin. Another convention places an informal dividing line at approximately 50 amino acids in length. This definition is somewhat arbitrary. Long polypeptides, such as the amyloid beta peptide linked to Alzheimer’s disease, can be considered proteins; and small proteins, such as insulin, can be considered peptides. At any rate, the skilled person will appreciate that essentially any type of polypeptide can be encapsulated and subsequently released from a copolymer matrix. The size of the polypeptide(s) can vary. In one embodiment, said polypeptide is a peptide with a molecular weight of 10000 Da or less. In another embodiment, said polypeptide is a protein having a molecular weight of 10000 Da or more. Polynucleotides, or nucleic acids, are macromolecules composed of nucleotide monomers that are covalently bonded in a chain. DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are examples of polynucleotides with distinct biological functions. Nucleotides are composed of a nitrogenous base, a five carbon sugar, and a phosphate group. Oligonucleotides are relatively short polynucleotide fragments (oligomers), usually 13-25 nucleotides long, although the maximum length of synthetic oligonucleotides can go up to 200 nucleotide monomers. Antisense oligonucleotides (ASO) are short, single stranded oligonucleotides that can alter RNA and reduce, restore, or modify protein expression through several distinct mechanisms. Pharmacologically active compounds can also be combinations of any of the foregoing, which includes, but is not limited to, the combinations of monoclonal antibodies and cytotoxic small molecule agents in antibody-drug conjugates (ADCs) used as targeted therapy for treating cancer. The multiblock copolymers of the invention have many options for tuning the release of the pharmacological active compound from the pharmaceutical composition for the specific application. The release rate of the pharmacologically active compound may for example be increased by: _{^ increasing the molecular weight of the water-soluble polyoxazoline polymer in} prepolymer (A) at constant molecular weight of prepolymer (A); _{^ increasing the block ratio between prepolymer (A) and prepolymer (B); ^ increasing the content of a monomer that gives a faster degrading polymer in} prepolymer (A) and prepolymer (B), e.g. by replacing ^-caprolactone by D,L-lactide or glycolide or by replacing D,L-lactide with glycolide; _{^ decreasing the molecular weight of prepolymer (A) at a constant molecular weight of the} water-soluble polyoxazoline polymer and block ratio between prepolymer (B) and prepolymer (A); and/or _{^ using of an additional, third segment derived from water-soluble polyoxazoline polymer,} whereby the content of the water-soluble polyoxazoline polymer is increased. The release rate may be decreased by the opposite changes as mentioned above. The at least one small molecule based pharmacologically active compound may be present in the matrix in an amount of 0.1-80 % by total combined weight of the matrix and the at least one small-sized drug molecule, in one embodiment 1.0-40 %, and in another embodiment 5-20 %. If it is desired to increase the hydrophilicity of the multiblock copolymer, and thereby increase the degradation rate of the copolymer and the release rate of the incorporated pharmacologically active compound, the copolymer may be modified by replacing partially or completely the D,L-lactide of the hydrophilic prepolymer (A) segment by glycolide and/or by using a POz component with a higher molecular weight or by increasing the weight fraction of POz component in the prepolymer (A) segment. If it is desired to decrease the hydrophilicity of the polymer, and thereby decrease the degradation rate of the copolymer, and the release rate of the incorporated pharmacologically active compound, the copolymer may be modified by replacing partially or completely the D,L-lactide of the hydrophilic prepolymer (A) segment by ^-caprolactone and/or by using a polyoxazoline water soluble polymer with a lower molecular weight or by decreasing the weight fraction of polyoxazoline water soluble polymer in the prepolymer (A) segment. In one embodiment, a composition of the invention comprises a pharmacologically active polypeptide or pharmacologically active polynucleotide. The size of the polypeptide(s) or polynucleotide can vary. In one embodiment, the polypeptide or polynucleotide has a molecular weight of 10000 Da or less. Polypeptides and polynucleotides of such size are particularly suitable to be encapsulated in the matrix of a copolymer comprising polyoxazoline as a segment of prepolymer (A) and/or as an additional prepolymer, said polyoxazoline having a number average molecular weight of 400-3000 g/mol, or in another embodiment 300-1500 g/mol. Alternatively, or in addition, said polyoxazoline can be present in an amount of 5-60 % by total weight of the copolymer, or in another embodiment 5-40 %. In another embodiment, said polypeptide or polynucleotide has a molecular weight of 10000 Da or more. These larger polypeptides or polynucleotides are in one embodiment encapsulated in the matrix of a copolymer which contains polyoxazoline, as a segment of prepolymer (A) and/or as an additional prepolymer, and wherein said polyoxazoline has a number average molecular weight of 400-5000 g/mol, or in another embodiment 1000-3000 g/mol. Alternatively, or in addition, said polyoxazoline can be present in an amount of 5-70 % by total weight of the copolymer, or in amount of 10-50 %. A composition of the invention can have any desirable appearance or shape. In one embodiment, multiblock copolymers of the current invention are processed in the form of microparticles, microspheres, microgranules, nanoparticles, nanospheres, rods, solid implants, gels, in situ forming implants, coatings, films, sheets, sprays, tubes, membranes, meshes, fibres, and plugs. One specific aspect relates to a composition in the form of microparticles. In general microparticles are small particles having a diameter of less than 1000 ^m, and containing a pharmacologically active compound. Spherical microparticles are also known as microspheres. The microparticle may be a homogeneous or monolithic microparticle in which the pharmacologically active compound is dissolved or dispersed throughout the polymer matrix. It is also possible that the microparticle is of a reservoir type in which the pharmacologically active compound is surrounded by a polymer in the mononuclear or polynuclear state. When the pharmacologically active compound is a small sized water-soluble drug, the drug may first be dispersed in a hydrophobic or lipophilic excipient, which combination then is dispersed in the form of particles, droplets, or micro-suspensions in the polymer matrix. Microspheres may be prepared by techniques known to those skilled in the art, including but not limited to coacervation, solvent extraction/evaporation, spray drying, spray-freeze drying, or spray congealing. In one embodiment, the microspheres are prepared by a solvent extraction/evaporation technique which comprises dissolving the multiblock copolymer in an organic solvent such as dichloromethane or ethyl acetate, and emulsification of the multiblock copolymer solution in an aqueous phase containing an emulsifying agent, such as polyvinyl alcohol (as described among others by Okada, Adv. Drug Deliver. Rev.1997, 28(1), 43-70). The characteristics, such as particle size, porosity and drug loading of the so formed microspheres depend on the process parameters, such as viscosity or concentration of the aqueous polyvinyl alcohol phase, concentration of the multiblock copolymer solution, ratio of dichloromethane to aqueous solution of active, ratio of primary emulsion to polyvinyl alcohol phase and the stirring rate. As the microspheres are being formed, the pharmacologically active compound is encapsulated in the microspheres or microparticles. In general, when the solvent extraction/evaporation technique is employed to encapsulate lipophilic compounds, the compound is first dissolved in a solution of the multiblock copolymer in an organic solvent such as dichloromethane or ethyl acetate. The organic solution is then subsequently emulsified in an aqueous polyvinyl alcohol solution, which yields an oil-in-water (O/W) emulsion. The organic solvent is then extracted into the aqueous phase and evaporated to solidify the microspheres. In general, when the solvent evaporation technique is employed to encapsulate water-soluble pharmacologically active compound, an aqueous solution of the compound is first emulsified in a solution of the multiblock copolymer in an organic solvent such as dichloromethane. This primary emulsion is then subsequently emulsified in an aqueous polyvinyl alcohol solution, which yields a water-in-oil-in-water (W/O/W) emulsion. The organic solvent, such as dichloromethane or ethyl acetate, is then extracted similarly to the O/W process route to solidify the microspheres. Alternatively, water-soluble pharmacologically active compounds may be dispersed directly in a solution of the multiblock copolymer in an organic solvent. The obtained dispersion is then subsequently emulsified in an aqueous solution comprising a surfactant such as polyvinyl alcohol, which yields a solid-in-oil-in-water (S/O/W) emulsion. The organic solvent is then extracted similarly to the O/W process route to solidify the microspheres. When W/O/W and S/O/W emulsification routes are used to encapsulate water soluble compound, it may be challenging to obtain microspheres with sufficient encapsulation efficiency. Due to the water soluble character of the compound, part of the compound may be lost to the aqueous extraction medium such as aqueous polyvinyl alcohol solution. A viscosifier, such as gelatine, may be used in the internal water phase, to decrease diffusion of the compound in the internal water phase to the external water phase. Also, additives may be added to the external water phase to decrease the solubility of the compound in the external water phase. For this purpose, salts may be used or the pH may be adjusted. Water-in-oil-in-oil (W/O/O) or solid-in-oil-in-oil (S/O/O) emulsification routes provide an interesting alternative to obtain microspheres with sufficient encapsulation efficiency. In the W/O/O process the pharmacologically active compound is, similar to a W/O/W process, dissolved in an aqueous solution and emulsified with a solution of the polymer in an organic solvent, such as typically dichloromethane or ethyl acetate. Subsequently, a polymer precipitant, such as silicon oil, is then slowly added under stirring to form embryonic microparticles, which are then poured into heptane or hexane to extract the silicone oil and organic solvent and solidify the microspheres. The microparticles may be collected by vacuum filtration, rinsed with additional solvent and dried under vacuum. In the S/O/O emulsification route the pharmacologically active compound is, similar to a S/O/W process, dispersed as a solid powder in a solution of the polymer in an organic solvent, such as dichloromethane or ethyl acetate. Subsequently, a polymer precipitant, such as silicon oil, is then slowly added under stirring to form embryonic microparticles, which are then poured into heptane or hexane to extract the silicone oil and dichloromethane and solidify the microspheres. Stabilising agents may be added to the aqueous solution of protein to prevent loss of protein activity during processing into microspheres. Examples of such stabilising agents are polyvinyl alcohol (PVA), Tween^®/polysorbatum, human serum albumin, gelatine and carbohydrates, such as trehalose, inulin and sucrose. When the microspheres are formed by spray-drying, a solution of polymer in an organic solvent, typically a volatile organic solvent such as dichloromethane, is employed. The concentration of the polymer solution is typically kept low, such as 0.5-5 % by total weight of the solution. In general, when spray-drying is employed to encapsulate lipophilic pharmacologically active compound, the pharmacologically active compound is directly dissolved in the polymer solution, after which the solution is spray-dried into microparticles. In general, when spray-drying is employed to encapsulate water-soluble pharmacologically active compound, such as peptides are proteins, the pharmacologically active compound may be dispersed in the organic solvent based polymer solution, after which the dispersion is spray-dried into microparticles. Alternatively, the water-soluble pharmacologically active compound may be first dissolved in an aqueous solution, followed by emulsification of the aqueous solution with the organic solvent-based polymer solution, after which the water-in-oil emulsion is spray-dried into microparticles using a spray dryer. When the microspheres are formed by spray-congealing, the polymer is processed in the molten state at sufficiently high temperature. When spray-congealing is employed, the pharmacologically active compound is either dissolved or dispersed in the molten polymer, whereafter the liquid mixture is atomised via a nozzle into droplets which are subsequently solidified into microparticles via cooling with air or gas in a chill tower. In one embodiment, the microparticles are obtained by grinding of premade formulations of the pharmacologically active compound and biodegradable copolymer, such as solid implants or strands prepared by hot melt extrusion or injection moulding. Such microparticles are also known as microgranules. Typically the microparticles, microgranules or microspheres have a volume based average diameter (D_v,50) between 10 and 150 ^m, preferably between 20 and 100 ^m, most preferably between 30 and 70 ^m. The amount of pharmacologically active compound incorporated in the microparticles, microgranules, or microspheres ranges generally 1-70 % by total weight of the composition, preferably 10-60 %, most 20-50 %. The microparticles, microgranules, or microspheres preferably contain 80-100 % by total weight of the microparticles, microgranules, or microspheres of the block copolymer and the at least one pharmacologically active compound. The amount of the at least one pharmacologically active compound is preferably 1-70 % by total weight of the microparticles, microgranules, or microspheres, more preferably 10-60 %, most preferably 20-50 %. In one embodiment, the composition is in the form of a solid implant. The active pharmaceutical ingredient may be formulated into solid implants via processes like for example hot melt extrusion or injection moulding. The active pharmaceutical ingredient can be incorporated in a biodegradable copolymer as a molecular blend or as a dispersion of solid particles. Typically, the pharmacologically active compound and multiblock copolymer powders are physically mixed, after which the resulting powder blend is introduced to the extruder, heated and processed to yield formulations of the desired shape and dimensions, such as a small diameter cylindrical rod or a film. Instead of physical mixing of the compound and multiblock copolymer powders, the pharmacologically active compound and polymer may be co-dissolved in a suitable solvent or a dispersion of compound in a solution of polymer in a suitable solvent may be prepared, followed by freeze-drying and extrusion of the freeze-dried powder. The latter generally improves the blend homogeneity and the content uniformity of the implants. In further embodiments, the implant may be a monolithic implant or an implant with one or more additional layers applied to a core implant, such as a coated implant, a dual layer implant or a core-sheath implant. The at least one pharmacologically active compound is typically incorporated in the core implant, and the function of the additional layer or layers is typically to control the release kinetics. The at least one pharmacologically active compound can also be incorporated in the additional layer. It is also possible that both the core implant and the additional layer contain at least one pharmacologically active compound. The additional layer or layers may be applied to the core implant via spray-coating, dip-coating or via co-extrusion or over-moulding. The solid implants preferably contain 80-100 % by total weight of the implants of the block copolymer and the at least one pharmacologically active compound. The amount of the at least one pharmacologically active compound is preferably 1-70 % by total weigh to of the implants, more preferably 10-60 %, most preferably 20-50 %. In a further embodiment, the composition of the invention is in the form of a solvent exchange in situ forming depot (ISFD). Such ISFDs may have an amount of multiblock copolymer of 20-50 % by total weight of the ISFD, preferably 30-40 %. The amount of pharmacologically active compound may be 1-50 % by total weight of the polymer and pharmacologically active compound together. The ISFD may further have a viscosity at 20 °C of 5 Pa∙s or less, preferably 2 Pa∙s or less, more preferably 1 Pa∙s or less, most preferably 0.5 Pa∙s or less. ISFD are preferably prepared of solutions of the polymer in a pharmaceutically acceptable organic solvent, such as N-methyl pyrrolidone, dimethyl sulphoxide, triacetin, benzyl benzoate or tripropionin, or combinations thereof, further containing a pharmacologically active ingredient. The pharmacologically active compound may be either dissolved or dispersed in the solution. Upon injection of the liquid formulation into an aqueous environment or into the body, the solvent is replaced by water leading to precipitation of the water-insoluble polymer, thereby forming a microporous, solid or gelatinous matrix with the pharmacologically active compound entrapped within the precipitated polymer matrix. The entrapped pharmacologically active compound is then released over a prolonged period of time by diffusion through the (porous) polymer matrix and by ongoing degradation and erosion of the polymer matrix. In further embodiments, the composition of the invention is in the form of a coating, an injectable gel, or a spray. The composition in the form of a coating may be applied as a drug-eluting coating e.g. on a medical implant, such as a vascular or urinary stent, an orthopaedic prosthesis or an ocular implant. In yet another aspect the invention is directed to a method of delivering a pharmacologically active compound to a subject in need thereof, comprising administering an effective dose of a composition as defined herein to said subject. The subject is typically a mammal, preferably a human. However, veterinary use of the invention is also encompassed. The method can have a therapeutic, prophylactic, and/or cosmetic purpose. Any suitable mode of administration can be selected, depending on the circumstances. For example, administering may comprise the parenteral, oral, intra-arterial, intra-articular, intravenal, intraocular, epidural, intrathecal, intramuscular, intraperitoneal, intravenous, intravaginal, rectal, topical or subcutaneous administration of the composition. In one embodiment, the invention provides a method for delivering a pharmacologically active compound of interest to a subject in need thereof, comprising administering an effective dose of a composition according to the invention to said subject, wherein the composition is in the form of microparticles, microspheres, or microgranules an injectable implant or an in situ forming gel and wherein the composition is administered intraocularly, intra-arterially, intramuscularly or subcutaneously. For topical administration, the microparticles may be contained in a gel, cream, or ointment, and may, if desired, be covered by a barrier. Thus, the microparticles may contain one or more pharmacologically active compounds employed in the treatment of skin diseases, such as psoriasis, eczema, seborrhoea, and dermatitis. In another embodiment, the microparticles may be contained in a gel such as a hyaluronic acid gel or a macromolecular polysaccharide gel. Such an embodiment is applicable particularly to parenteral applications, such as during and after surgery. When administered via injection, the microparticles may be contained in a pharmaceutical carrier such as water, saline solution (for example, 0.9 %), or a solution containing a surfactant in an amount of from 0.1-0.5 % w/v. Examples of surfactants which may be employed include, but are not limited to, Tween^® 80 surfactant. The pharmaceutical carrier may further contain a viscosifier, such as sodium carboxymethylcellulose. Such microparticles, when administered in combination with an acceptable pharmaceutical carrier, may be employed in the treatment of a variety of diseases or disorders, depending upon the pharmacologically active compound that is encapsulated. In one aspect, provided herein are injectable delivery systems comprising a multiblock copolymer as described herein. The multiblock copolymer can be in the form of an implant. Such implant may be a microsphere, a rod, a film, a multiblock copolymer depot, or a plurality thereof. The multiblock copolymer may in the form of a plurality of polymeric microspheres that are each not less than 20 ^m in diameter, wherein the polymeric microspheres comprise the multiblock copolymer as described herein. The polymeric microspheres can be 20-80 ^m in diameter, such as 30-70 ^m in diameter. The polymeric microspheres may be monodisperse with a coefficient of variation of about 25 %. The injectable delivery systems may further comprise a therapeutic agent, or a pharmaceutically acceptable salt thereof. The therapeutic agent may be a small chemical, a protein, an antibody, a peptide or an oligonucleotide, or a combination thereof. Additionally, the injectable delivery systems can further comprise a pharmaceutically acceptable excipient. The invention further relates to a pharmaceutical composition comprising a biodegradable, thermoplastic multiblock copolymer of the invention. Such a pharmaceutical composition can be in the form of microspheres, microparticles, nanoparticles, nanospheres, rods, solid implants, gels, in situ forming implants, coatings, films, sheets, sprays, tubes, membranes, meshes, fibres, scaffolds or plugs. Preferably, the pharmaceutical composition further comprises at least one pharmacologically active compound encapsulated in the matrix of the biodegradable, thermoplastic multiblock copolymer, and which pharmacologically active compound can be controllably released after insertion in a human or animal. The invention has been described by reference to various embodiments, compositions and methods. The skilled person understands that features of various embodiments, compositions and methods can be combined with each other. All references cited herein are hereby completely incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein. The use of the terms “a” and “an” and “the” and similar referents in the context of describing the invention (especially in the context of the claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms “comprising”, “having”, “including” and “containing” are to be construed as open ended terms (i.e., meaning “including, but not limited to”) unless otherwise noted. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention. For the purpose of the description and of the appended claims, except where otherwise indicated, all numbers expressing amounts, quantities, percentages, and so forth, are to be understood as being modified in all instances by the term “about”. Also, all ranges include any combination of the maximum and minimum points disclosed and include any intermediate ranges therein, which may or may not be specifically enumerated herein. For the purpose of clarity and a concise description features are described herein as part of the same or separate embodiments, however, it will be appreciated that the scope of the invention may include embodiments having combinations of all or some of the features described. EXAMPLES The invention will now be further illustrated by the following non-limiting examples. In the following examples, various biodegradable thermoplastic amorphous polyoxazoline-based copolymers were synthesised and evaluated for their processability into long-acting injectable drug delivery formulations, their drug release characteristics and their erosion characteristics. The polymers were composed of an amorphous polyoxazoline-based polyester prepolymer (A) segment with a relatively high Tg and a prepolymer (B) segment comprising a polyester polymer block. Example 1 In accordance with the invention, the water-soluble PEG in the biodegradable multiblock copolymers with low Tg (-40 to -50 °C) used in the prepolymer segment (A) is replaced with water-soluble polyoxazoline with high Tg (40-60 °C). The crystalline prepolymer segment (B) is replaced with fast degrading amorphous poly (D,L-lactide) or poly(glycolide-co-lactide) with Tg of 35 to 55 °C. The resulting polyoxazoline-based copolymers possess a Tg > 30 °C, depending on the composition of the hydrophilic polyoxazoline prepolymer segment (A) and amorphous prepolymer segment (B). The mechanical characteristics of the copolymer will to a large extent be determined by the high Tg domains, similar as observed for semicrystalline phase separated multiblock copolymers of WO-A-2012/005594 and WO-A-2013/015685. The prepolymer segment (A) and prepolymer segment (B) phase mix in the multiblock copolymer to yield a single Tg between individual Tgs of the prepolymers. The resulting Tg of the multiblock copolymer can be sufficiently high, such as around 30 °C or higher. The high Tg hydrophilic polyoxazoline (will be referred to as “POz”) based prepolymer segment (A) was synthesised in two steps, 1) synthesis of difunctional POz block (diol) by cationic ring-opening polymerisation and 2) use the POz diol from the step 1 as an initiator for ring opening polymerisation of cyclic monomers that yields POz based prepolymer segment (A). In step 1, methyl p-toluene sulphonate and 2-ethyl-2-oxazoline (EOz) were distilled and stored under a nitrogen atmosphere before use. 2-Ethyl-2-oxazoline was stored under molecular sieves (4A). Anhydrous acetonitrile (300 ml) and 2-ethyl-2-oxazoline (100 ml, 98.2 g, 0.99 mol) were added to a pre-dried 500 ml round bottom flask and heated in an oil bath to 80 °C and stirred using a magnetic stir bar. The reaction was started by adding methyl p-toluene sulphonate (31.49 g, 0.17 mol) and stirring continued for 18 h at 80 °C. The temperature was lowered to 50 °C upon reaction completion (checked using ¹H-NMR), then quenched by the addition of diethanolamine (53.21 g, 0.50 mol) to the reaction mixture and reacted for a further 18 h at 50 °C. After cooling down to room temperature, the solvent was removed under reduced pressure. The residue was dissolved in 1200 ml of dichloromethane and washed twice with 15 wt.% brine (2 × 1200 ml). The organic layer was dried in Na2SO4, filtered using a sintered glass funnel and passed through a charcoal column protected with celite pads under suction. The solvent was evaporated to yield POz diol of molecular weight 600 g/mol as a white powder, hereafter called POz6. Similarly, POz10, POz20 and POz30 diols with target Mn of 1000, 2000 and 3000 g/mol respectively were prepared. In step 2, the POz-based prepolymer poly(^-caprolactone)-co-POz6-co-poly(^-caprolactone) with a target Mn of 1200 g/mol (abbreviated as ppCPOz6C12) was prepared by ring-opening polymerisation of ^-caprolactone (CL) using POz6 diol as an initiator. Briefly, ^-caprolactone (Acros Organics) was dried and distilled over CaH2 under reduced pressure and stannous octoate (Sigma Corp.) was purified by vacuum distillation. About 26.07 g (0.04 mol) of POz6 was weighed into a 250 ml three-necked round bottom flask and dried at 60 °C under pressure for 18 h and then 26.18 g (0.23 mol) of distilled ^-caprolactone was added to the POz6 under nitrogen atmosphere. Distilled toluene (52.67 g) was added to the flask and heated to 110 °C to dissolve the reactants. Subsequently, 2.10 g of stannous octoate 1 wt.% solution in toluene was added and stirring continued at 110 °C until conversion was > 98 % as confirmed by ¹H-NMR. The toluene was removed under reduced pressure using a rotary evaporator and the prepolymers were stored as 50 wt.% solution in dioxane under a nitrogen atmosphere. The molecular weight as determined by ¹H-NMR was ~ 1200 g/mol. Similarly, CPOz10C20, CPOz20C30 and CPOz30C40 with target Mn of 2000, 3000 and 4000 g/mol respectively were prepared. The amorphous prepolymer segment (B) poly(D,L-lactide) with a target Mn of 4000 g/mol (abbreviated as ppL40) was synthesised in bulk by 1,4-butanediol (BDO) initiated ring-opening polymerisation. BDO (Acros Organics) was distilled over CaH2 under reduced pressure and stored under a nitrogen atmosphere until further use.509.6 g (3.53 mol) of D,L-lactide (L) (Purac, Corbion N.V.) was weighed into a three-necked flask under a nitrogen atmosphere and dried at 50 °C for at least 16 h under reduced pressure. Subsequently, 11.4 g (0.13 mol) BDO was added to the monomer under a nitrogen atmosphere. The mixture was heated to 140 °C giving a clear molten fluid.62 mg of stannous octoate was added as 1.0 wt.% solution in p-dioxane (Acros, dried and distilled), starting the ring-opening polymerisation. After 20 h the reaction was cooled down to room temperature.¹H-NMR showed 97.0 % monomer conversion. Similarly, poly(D,L-lactide) with a target Mn of 2000 g/mol (abbreviated as ppL20) was prepared. Table 1 and 3 shows the molecular weight of ppL40 and L20 determined by ¹H-NMR. [Poly(ε-caprolactone)-co-POz-co-poly(ε-caprolactone)]−b− poly(D,L-lactide) copolymers with block ratios of 10/90 w/w (hereafter abbreviated as 10CPOz6C12-L20) and 20 / 80 (hereafter abbreviated as 20CPOz6C12-L20) were synthesised by chain-extending the diol-functionalised CPOz6C12 with L20 using 1,4-butane diisocyanate as a chain extender. In brief, ppL20 was weighed into the reactor and dried for 18 h under reduced pressure at 90 °C. After drying, 50 wt.% solution of ppCPOz6C12 in dioxane was added. Water free distilled p-dioxane was added into the reactor until a polymer concentration of 30 wt.% was reached. The reactor was heated to 80 °C to dissolve the prepolymers and once a homogeneous solution was obtained, 1,4-butane diisocyanate (BDI) (Actu-All Chemicals) was added. Additional stannous octoate was added to increase its total content to 50-120 ppm and the reaction mixture was stirred mechanically until the desired viscosity was obtained, where after distilled p-dioxane containing 20 wt.% water was added. Stirring was continued for an additional 30 min. The reaction mixture was further diluted with p-dioxane to a polymer concentration of 20 wt.%, cooled to room temperature, and poured into a tray, and frozen at -20 °C after which p-dioxane was removed from the frozen solution under reduced pressure yielding dry polymer. Using similar procedures, various xxCPOzyyCzz-L40 copolymers were prepared by chain-extending ppCPOzyyCzz prepolymer _{with L40 prepolymer in a 10 / 90 w/w ratio using BDI as a chain extender. Table 1 lists the} experimental details of the various [poly(ε-caprolactone)-co-POz-co- poly(ε-caprolactone)]−b−poly(D,L-lactide) copolymers. Polymers were analysed for polymer composition (¹H-NMR), intrinsic viscosity _{and thermal properties (mDSC) as described in Example 2. Table 2 shows the results from} the characterisation of the prepared copolymers. Table 1. Experimental details of [poly(ε-caprolactone)-co-POz-co- poly(ε-caprolactone)]−b−[poly(D,L-lactide)] copolymers ppCPOzyyCzz L20 or L40 BDI Grade POz Mn Mn Mn Batch (g) (g) (g) (g/mol) (g/mol) (g/mol) 10CPOz6C12-L20 R031-2213 794 8.0 1200 72.2 2032 5.01 20CPOz6C12-L20 R031-2212 794 15.9 1200 64.0 2032 5.00 10CPOz10C20-L40 EH-2001-84 1210 10.1 2000 90.0 3869 4.29 20CPOz10C20-L40 EH-2001-94 1013 20.2 2000 81.6 3869 3.75 10CPOz20C30-L40 R031-2217 1739 8.0 3000 72.0 3999 2.58 30CPOz30C40-L40 GK-2101-40 2900 37.8 4000 102.2 4167 4.46

Table 2. Chemical composition, intrinsic viscosity and thermal characteristics of [poly(ε-caprolactone)-co-POz-co-poly(ε-caprolactone)]−b−poly(D,L-lactide) copolymers POz Monomer ratio Monomer ratio IV Tg Grade content (in-weights) (¹H-NMR) Batch (dl/g) (°C) (wt.%) (mol/mol) (mol/mol) CL / EOz = 0.9 CL / EOz = 1.0 10CPOz6C12-L20 R031-2213 5 0.38 40 L / EOz = 23.9 L / EOz = 25.0 CL / EOz = 0.9 CL / EOz = 1.1 20CPOz6C12-L20 R031-2212 10 0.39 34 L / EOz = 10.6 L / EOz = 11.1 CL / EOz = 0.9 CL / EOz = 0.9 10CPOz10C20-L40 EH-2001-84 5 0.79 46.5 L / EOz = 24.8 L / EOz = 25.2 CL / EOz = 0.9 CL / EOz = 1.0 20CPOz10C20-L40 EH-2001-94 10 0.73 39 L / EOz = 11.0 L / EOz = 12.2 CL / EOz = 0.3 CL / EOz = 0.3 10CPOz20C30-L40 R031-2217 6.6 0.58 45 L / EOz = 16.2 L / EOz = 15.4 CL / EOz = 0.5 CL / EOz = 0.4 20CPOz20C30-L40 R031-2307 13.3 0.63 44 L / EOz = 8.6 L / EOz = 8.1 CL / EOz = 0.5 CL / EOz = 0.4 30CPOz20C30-L40 R031-2308 20 0.65 42 L / EOz = 5.0 L / EOz = 4.7 CL / EOz = 0.4 CL / EOz = 0.3 30CPOz30C40-L40 GK-2101-40 22.5 0.75 42.5 L / EOz = 4.8 L / EOz = 4.1 Example 2 This example describes the analytical methods used for the characterisation of p_{repolymers and final copolymers. 1H-NMR was performed on a Bruker Avance DRX 500} MHz NMR spectrometer (B AV-500) equipped with Bruker Automatic Sample Changer (BACS 60) (Varian) operating at 500 MHz. The d1 waiting time was set to 20 s, and the number of scans was 16. Spectra were recorded from 0 to 14 ppm. The conversion in prepolymers and the block ratio in copolymers were determined from ¹H-NMR. The prepolymer Mn was determined from both in-weights and ¹H-NMR.¹H-NMR samples were prepared by adding 1.3 g of deuterated chloroform to 25 mg of polymer. The intrinsic viscosity of MBCPs was measured using an Ubbelohde Viscosimeter (DIN), type 0C, Si Analytics supplied with a Si Analytics Viscosimeter including a water bath. The measurements were performed in chloroform at 25 °C. The polymer concentration in chloroform was such that the relative viscosity was in the range of 1.2-2.0 dl/g. Gel Permeation Chromatography (GPC) analysis was used to determine number average molecular weights and weight average molecular weights of multiblock copolymers, and was performed by a PSS Security system (Agilent, Middelburg, The Netherlands), equipped with a differential refractive index detector. Separation was performed by a column set, consisting of two sdv analytical columns (Agilent, Middelburg, The Netherlands), both 30 cm × 8.0 mm ( L × I.D.) with pore sizes of 1000 Å and 100000 Å, and a sdv analytical pre-column, 30 cm × 8.0 mm ( L × I.D.). The column set was maintained at a constant temperature of 35 °C. The isocratic mobile phase consisted of a chloroform : triethylamine (99.9 : 0.1, v/v) mixture and has a flow rate of 1.00 ml/min. Samples were dissolved in a 1 mg/ml of butylated hydroxy toluene in a chloroform : triethylamine (99.9 : 0.1, v/v) mixture, and were filtered over a 0.45 ^m PTFE filter.50 ^l of the filtrate was injected into the system. The system was calibrated by injecting narrow polymer reference standards (polymethyl methacrylate) varying in Mp range from 0.6 KDa – 2 MDa, defining also the lowest and highest quantifiable masses. Equipment control, data acquisition and data processing was performed by PSS WinGPC, version 8.20. Modulated differential scanning calorimetry (mDSC) was used to determine the thermal behaviour of the prepolymers and multiblock copolymers using a Q2000 MDSC (TA instruments, Ghent, Belgium). About 4-8 mg of dry material was accurately weighed and heated under a nitrogen atmosphere from -85 °C to 100 °C at a heating rate of 2 °C/min and modulation amplitude of +/- 0.42 °C every 80 s. The glass transition temperature (Tg, midpoint) was determined from the reversing heat flow. Temperature and enthalpy were calibrated with an indium standard. Example 3 This example describes the preparation of poly(glycolide-co-L-lactide) with a target Mn of 4000 g/mol (abbreviated as ppGLL40). ppGLL40 was prepared by ring-opening copolymerisation of L-lactide (LL) and glycolide (G) using BDO as an initiator. 653.16 g (9.06 mol) of L-lactide (Purac, Corbion N.V.) and 92.78 g (1.59) mol) of glycolide (Purac, Corbion N.V.) were added into a three-necked flask under nitrogen and dried at 50 °C for at least 16 h under reduced pressure. When dried, 16.35 g (0.18 mol) of distilled BDO was added to the monomers under a nitrogen atmosphere and the reactants were dissolved in 762 g of p-dioxane at 90 °C to obtain 50 wt.% solution. Once the clear solution is obtained, 116.4 mg of distilled stannous octoate was added as 1 wt.% solution in distilled p-dioxane. The reaction was stirred for an additional 140 h and cooled down when conversion reached 94.9 %. The molecular weight is shown in Table 3 as determined by ¹H-NMR. Example 4 This example describes the preparation of POz-based prepolymer poly(D,L-lactide)-co-POz-co-poly(D,L-lactide) with a target Mn of 3000 g/mol (abbreviated as ppLPOz10L30) by ring-opening polymerisation of D,L-lactide using POz10 diol as an initiator. Briefly, 41.07 g (0.04 mol) of POz10 and 83.06 g (1.15 mol) were weighed into a 250 ml three-necked round bottom flask and dried at 60 °C under vacuum for 18 h. Water-free distilled p-dioxane was added into the flask until a polymer concentration of 50 wt.% was reached and the temperature was set to 95 °C to dissolve the prepolymers. Once homogeneous, 4.7 g of stannous octoate 1 wt.% solution in dioxane was added and stirring continued at 95 °C until conversion was 94 % as confirmed by ¹H-NMR. The prepolymer solution was cooled down at the end of the reaction and stored as 50 wt.% solution in dioxane under a nitrogen atmosphere. The molecular weight as determined by ¹H-NMR was ~ 3000 g/mol. Similarly, LPOz6L12, LPOz10L20 and LPOz20L50 with target Mn of 1200, 2000 and 5000 g/mol respectively were prepared. Example 5 This example describes the synthesis and characterisation of [Poly(D,L- lactide)-co-POz-co-poly(D,L-lactide)]−b−poly(D,L-lactide) multiblock copolymer with a block ratio of 10 / 90 w/w (10LPOz6L12-L20).10LPOz6L12-L20 was prepared by chain-extension of 127.24 g of ppL20 prepolymer with Mn of 2000 g/mol with 27.88 g of ppLPOz6L12 prepolymer with Mn of 1200 g/mol using 7.03 g BDI as a chain extender. After drying ppL20 in a flange glass reactor, a 50 wt.% dioxane solution of ppLPOz6L12 was added and dissolved in distilled p-dioxane to a final concentration of 30 wt.% after which reaction mixture is heated to 80 °C and BDI was added. Chain extension, work-up and drying of 10LPOz6L12-L20 were performed according to the procedures as described in Example 1. Table 3. Experimental details of [poly(D,L-lactide)-co-POz-co-poly(D,L-lactide)]−b−poly(D,L-lactide) copolymers ppL20 or L40 or ppLPOzL GLL40 BDI Grade Batch POz Mn Mn Mn (g) (g) (g) (g/mol) (g/mol) (g/mol) 10LPOz6L12-L20 IT-2001-109 777 1200 127.2 1957 7.03 13.9 20LPOz6L12-L20 RCP-2135 724 28.3 1200 112.8 1957 9.32 10LPOz10L20-L40 IT-2001-065 1194 28.3 2000 125.9 3869 5.16 20LPOz10L20-L40 RCP-2128 1113 28.5 2000 114.1 4122 5.22 20LPOz20L50-L40 R031-2207 1925 16.2 5000 63.7 4057 2.38 30LPOz10L20-L40 EH-2001-80 1178 41.1 2000 95.7 3869 5.95 30LPOz10L30-L40 R031-2208 1111 30.3 3000 69.9 4057 3.39 30LPOz20L50-L40 R031-2209 1925 21.5 5000 49.3 4057 2.07 40LPOz10L30-L40 GK-2101-030 1113 68.5 3000 66.6 4050 3.95 20LPOz10L20-GLL40 R031-2201 1155 22.8 2000 91.1 4187 4.12 (15 / 85) 40LPOz10L30-GLL40 R031-2211 1111 31.8 3000 47.7 4199 2.77 (15 / 85) 60LPOz10L30-GLL40 RCP-2311A 1098 210.1 3000 140.0 4212 2.86 (15 / 85) 50LPOz10L30-L40 R031-2206 1111 49.7 3000 49.7 4057 3.65 Polymers were analysed for chemical composition (¹H-NMR), intrinsic viscosity and thermal properties (mDSC) as described above. Table 4 shows the analysis results for prepared copolymers. Table 4. Chemical composition, intrinsic viscosity and thermal characteristics of [poly(D,L-lactide)-co-POz-co-poly(D,L-lactide)]−b− poly(D,L-lactide) copolymers Monomer POz Monomer ratio ratio IV Tg Grade Batch content (¹H-NMR) (in-weights) (dl/g) (°C) (wt.%) (mol/mol) (mol/mol) 10LPOz6L12-L20 IT-2001-109 5 L / EOz = 25.4 L / EOz = 24.1 0.32 43 20LPOz6L12-L20 RCP-2135 10 L / EOz = 12.4 L / EOz = 13.9 0.39 42 10LPOz10L20-L40 IT-2001-065 5 L / EOz= 26.1 L / EOz = 24.5 0.65 50 20LPOz10L20-L40 RCP-2128 10 L / EOz = 12.4 L / EOz = 12.5 0.57 52 20LPOz20L50-L40 R031-2207 8 L / EOz = 15.8 L / EOz = 17.1 0.61 43 30LPOz10L20-L40 EH-2001-80 15 L / EOz = 7.8 L / EOz = 8.6 0.93 51 30LPOz10L30-L40 R031-2208 10 L / EOz = 12.4 L / EOz = 12.7 0.68 44 30LPOz20L50-L40 R031-2209 12 L / EOz = 10.2 L / EOz = 10.0 0.72 50.5 40LPOz10L30-L40 GK-2101-030 13.3 L / EOz = 8.7 L / EOz = 10.6 0.63 45 20LPOz10L20-GLL40 L / EOz = 10.8 L / EOz = 10.5 R031-2201 10 0.60 51 (15 / 85) G / EOz = 0.9 G / EOz = 1.8 40LPOz10L30-GLL40 L / EOz = 8.2 L / EOz = 9.1 R031-2211 13.3 0.61 54 (15 / 85) G / EOz = 0.5 G / EOz = 1.2 60LPOz10L30-GLL40 L / EOz = 4.5 L / EOz = 4.5 RCP-2311A 20 0.61 51 (15 / 85) G / EOz = 0.4 G / EOz = 0.5 50LPOz10L30-L40 R031-2206 16.6 L / EOz = 6.9 L / EOz = 7.6 0.71 48.5 Example 6 This example depicts the synthesis of POz copolymer using linear ^,^-hydroxyl terminated poly(2-ethyl-2-oxazoline) prepared as follows. A three-neck flask was dried and placed under N2 atmosphere. The recrystallised trans-1,4-dibromo-2-butene was weighed in the three-neck flask and dried with high vacuum for 2 h at room temperature. Subsequently, distilled ACN and EOz were added to the three-neck flask. The reaction was carried out at 80 °C overnight under N2 atmosphere and subsequently the reaction mixture was cooled down in an ice bath. Tetramethylammonium hydroxide solution in methanol (25 wt.%) was added to the three-neck flask to terminate the reaction. The reaction was carried out overnight. The next day, the reaction mixture was filtered and ACN was removed using a rotavapor. DCM was added to the flask, and the resulting mixture was filtered under vacuum. Polymer solution in DCM was further washed twice with 15 wt.% NaCl aqueous solution. The obtained organic phase was dried over anhydrous Na2SO4 and filtered through a column filled with activated charcoal and Celite. Finally, the solvent was evaporated to yield POz as a white powder. POz-based prepolymer poly(D,L-lactide)-co-POz-co-poly(D,L-lactide) with a target Mn of 4000 g/mol (abbreviated as ppLPOz30L40) was prepared by ring-opening polymerisation of D,L-lactide using ^,^-hydroxyl terminated POz30 diol as an initiator. Briefly, 41.32 g of POz30 and 13.09 g of D,L-lactide were weighed into a 250 ml three-necked round bottom flask and dried at 60 °C under vacuum for 18 h. Water-free distilled chlorobenzene was added into the flask until a polymer concentration of 50 wt.% was reached and the temperature was set to 120 °C to dissolve the prepolymers. Once homogeneous, 56 mg of tin octanoate was added and stirring continued at 120 °C until conversion was 94 % as confirmed by ¹H-NMR. The prepolymer solution was cooled down at the end of the reaction and chlorobenzene is evaporated under vacuum to yield off-white polymer foam. The obtained prepolymer was used for the preparation of [poly(D,L-lactide)-co-POz-co-poly(D,L-lactide)]−b−poly(D,L-lactide) multiblock copolymer with a block ratio of 10 / 90 w/w (10LPOz30L40-L40).10LPOz30L40-L40 was prepared by chain extension of 125.50 g of ppL40 prepolymer with Mn of 4000 g/mol with 13.94 g of ppLPOz30L40 prepolymer with Mn of 4000 g/mol using 4.59 g BDI as a chain extender. After drying both polymers in jacketed reactor, polymers were dissolved in distilled p-dioxane to a final concentration of 30 wt.% after which reaction mixture is heated to 80 °C and BDI was added. Chain extension, work-up and drying of 10LPOz30L40-L40 were performed according to the procedures as described in Example 1. The prepared polymer had an intrinsic viscosity of 0.64 dl/g, a L / EOz monomer ratio of 18.5 mol/mol and a Tg of 50 °C. Example 7 The glass transition temperatures (Tg) of both PEG-based copolymers and POz-based copolymers of the same structure are using the Fox equation: where ^^_^^ and ^^_^^ are weight fractions of prepolymers A and B, respectively. The homopolymer values used for calculation are given in Table 5. Table 5. Glass transition temperatures of individual polymer components Polymer component Tg (°C) PEG -52 POz 50 Poly(D,L-lactide) 50 P_{oly(glycolide-co-L-lactide) 55} Poly(^-caprolactone) -60 Based on the Tg contribution of POz as compared to PEG, it can be predicted that the Tg of multiblock copolymers will significantly increase by replacing PEG as hydrophilic moiety in the prepolymer (A) segment by POz. The Tg of the POz-based multiblock copolymers in dry state were measured using modulated DSC (mDSC) and compared with PEG-based multiblock copolymers with the same overall composition (except that they contained PEG instead of POz) and with the same content of hydrophilic moiety (PEG or POz) (Table 6). Table 6. Glass transition comparison between PEG and POz polymers POz / PEG Grade Grade Tg (°C) Tg (°C) wt.% PEG-polymer POz-polymer 10LP6L12-L20 10LPOz6L12-L20 5 36 43 (RCP-2119, 2222) (IT-2001-109) 20LP6L12-L20 20LPOz6L12-L20 10 29 42 (RCP-2125) (RCP-2135) 30CP30C40-L40 30CPOz30C40-L40 22.5 3 43 (R031-2311) (GK-2001-43) 60LP10L30-L40 60LPOz10L30-GLL50 20 15 51 (R031-2315) (RCP-2311) For all POz-based multiblock copolymers a higher Tg was obtained as compared to PEG-based multiblock copolymers with the similar overall composition (except for the type of hydrophilic moiety, POz or PEG). Interestingly, no change in Tg was observed by increasing content of LPOz6L12 block. Thus, replacement of PEG with POz in copolymers allows preparation of high Tg polymers which has several benefits for long-acting injectable dosage forms. Example 8 To study the erosion kinetics of the POz-based copolymers, polymer-only microspheres were prepared by solvent extraction/evaporation based oil-in-water emulsification.5.8 g of polymer dissolved in 52.4 g of dichloromethane (10.0 wt.%) was emulsified in 3.08 kg of ultrapure water containing 0.4 wt.% PVA and 5 wt.% NaCl via membrane emulsification using a membrane with a pore size of 20 ^m. The resulting microspheres were collected on a 5 ^m membrane filter and washed three times with 250 ml of ultrapure water containing 0.05 wt.% of Tween^® 80 and three times with 250 g of ultrapure water. Finally, the microspheres were lyophilised. The structural changes of the POz-based microspheres over time were followed _{using 1H-NMR. 1H-NMR was performed on a Bruker Avance DRX 500 MHz NMR} spectrometer (B AV-500) equipped with Bruker Automatic Sample Changer (BACS 60) (Varian) operating at 500 MHz. The d1 waiting time was set to 20 s, and the number of scans was 16. Spectra were recorded from 0 to 14 ppm.¹H-NMR samples were prepared by adding 1.3 g of deuterated chloroform to 25 mg of polymer. The particle size distribution of the microspheres was measured by laser diffraction (Horiba^® LA-960 Laser Particle Size Analyser). Microspheres were suspended in water until transmittance was within 70-90 % and the particle size distribution of the suspension was determined within the range of 10 nm – 5000 ^m. The surface morphology of the microspheres was evaluated by scanning electron microscopy, using a JEOL JCM-5000 Neoscope. A small amount of microspheres was adhered to carbon conductive tape and coated with gold for 3 min. The sample was imaged using a 10 kV electron beam. The in vitro erosion of non-loaded polymer-only microspheres was measured in 100 mM of phosphate buffer pH 7.4 (90-100 mg of microspheres in 10 ml). The samples were incubated at 37 °C. At each sampling point, the microspheres were collected, freeze-dried and weighed. All POz-based copolymers were well processable into polymer-only microspheres yielding non-porous particles with a smooth surface. No agglomeration was observed. The volume average particle size distribution (Dv,50) of the microspheres is shown in Table 7. Note that polymer PEG-based multiblock copolymer 20LP10L20-GLL40 (15 / 85) was used as a direct comparison to POz-based copolymer. Table 7. Size characteristics of prepared microspheres for IVD testing POz content Dv,50 * CV Batch code Polymer grade (%) (^m) (%) R036-220322 20LPOz10L20-GLL40 (15 / 85) 10 44 25 R036-220323 20LP10L20-GLL40 (15 / 85) 10 55 44 R036-220325 40LPOz10L30-L40 13.3 47 25 * Dv,50 means volume average particle size The remaining weight of tested microspheres is plotted in Figure 1. The first result that strikes is related to overlapping of the weight loss curve for both 20LPOz10L20-GLL40 (15 / 85) and 20LP10L20-GLL40 (15 / 85). The main reason for such behaviour might lay in similar swelling abilities of both polymers, which also explains the close similarities of ropivacaine release curves from both PEG-based microspheres and POz-based microspheres as described in Example 9. Contrary to 20LPOz10L20-GLL40 (15 / 85), 40LPOz10L30-L40 demonstrated significantly faster degradation, with most of the polymer degraded within only two months. This is attributed to the higher content of hydrophilic block which allows higher water influx and faster degradation. SEM micrographs of microspheres based on 20LPOz10L20-GLL40 and 20LP10L20-GLL40 taken after two and six months demonstrate similar behaviour of both polymers regarding in vitro degradation (Figure 2). No obvious changes for both batches was observed after two months. The further degradation leads to a reduction in size and change in shape of the microspheres for both polymers. Conversely, the more swellable polymer 30LPOz20L50-L40 shows a different behaviour. After two months, an increase in microsphere diameter was observed. Over time, microspheres lost their mechanical integrity and started to fragment. An obvious increase of diameter is observed as well for 40LPOz10L30-L40 after one month. However, after two months, no sample was left after centrifugation and freeze drying to be analysed, thus more specific knowledge on degradation of this polymer is unavailable. Table 8 shows GPC results of all investigated polymers at the beginning of the study and after six months of in vitro degradation. As in case of remaining weight analysis and SEM, polymers 20LPOz10L20-GLL40 and 20LP10L20-GLL40 portray similar molecular weight of remaining oligomers after 6 months. Table 8. Molecular weight (Mn, Mw) as determined by GPC of polymer-only microspheres prepared of POz-based copolymers after six months of degradation Sample R036-220322 R036-220323 R036-220325 point 20LPOz10L20-GLL40 20LP10L20-GLL40 40LPOz10L30-L40 (months) (G / LL = 15 / 85) (G / LL = 15 / 85) Mw = 59.0 kDa Mw = 90.5 kDa Mw = 83.7 kDa 0 Mn = 22.8 kDa Mn = 33.8 kDa Mn = 35.8 kDa D = 2.59 D = 2.68 D = 2.37 Mw = 1.76 kDa Mw = 1.69 kDa 6 Mn = 1.2 kDa Mn = 1.15 kDa N.A. D = 1.46 D = 1.48 To further elucidate the mechanism behind the degradation of POz-based copolymers, ¹H-NMR of microspheres was taken after two and six months and compared to the initial polymers. The obtained results are given in Table 9. The ¹H-NMR results demonstrated fast reduction of the POz content inside the microspheres after two months, which further reduced over time. At six months the POz polymer was fully excreted from microspheres. A similar, though slower, reduction of PEG content was observed for the microspheres prepared of the PEG-based multiblock copolymer. The content of glycolide compared to lactide inside both polymers reduced overtime, which is expected, since glycolide has higher hydrophilicity compared to L-lactide. Microspheres composed of 40LPOz10L30-L40 showed a significantly faster reduction of the POz content inside the microspheres, and thus faster degradation. Table 9. Composition of microspheres during in vitro degradation obtained using ¹H-NMR Sample R036-220322 R036-220323 R036-220325 point 20LPOz10L20-GLL40 20LP10L20-GLL40 40LPOz10L30-L40 (months) (G / LL = 15 / 85) (G / LL = 15 / 85) POz L G PEG L G POz L (wt.%) (wt.%) (wt.%) (wt.%) (wt.%) (wt.%) (wt.%) (wt.%) 0 ^{10.3 78.3} 11.4 12.7 77.4 9.9 13.7 86.3 2 ^{2.7 87.7} _{9.6 5.8 84.4 9.8 1.1 98.9} 6 ^{0.0 91.9} 8.1 2.1 91.4 6.4 n.a.. n.a. Example 9 Ropivacaine-loaded microspheres with a target loading of 50 wt.% were prepared via oil-in-water (O/W) membrane emulsification followed by solvent extraction/evaporation.1.0 g of polymer and 1.0 g of ropivacaine base were dissolved in dichloromethane (DCM) to a final polymer concentration of 15 wt.% to form the dispersed phase (DP). Following filtration over a 0.2 ^m polytetrafluoroethylene (PTFE) filter, DP was emulsified with an aqueous solution containing 0.4 wt.% PVA and 5 wt.% NaCl (continuous phase (CP)) via a membrane with 20 ^m pores. The formed O/W emulsion was stirred for 2 h at room temperature followed by 1 h at 40 °C under an airflow of 5 l/min to extract and evaporate DCM and harden the microspheres. After completion of solvent evaporation and cooling down to room temperature, the hardened microspheres were collected by filtration and washed three times with 250 ml 0.05 wt.% Tween^® 80 solution and three times with 250 ml WFI (Water For Injection), after which the microspheres were lyophilised. _{Table 10. List of prepared ropivacaine-loaded MSP} POz _{PSD (^m) ** Drug} POz Mn EE Batch # POz-MBCP grade content Dv,50 CV content (g/mol) (%) (wt.%) (^m) (%) (wt.%) R036-210462 20LP10L20-GLL40 - * - * 39 22.1 43.0 85.3 R036-210615 20LPOz10L20-L40 1000 10 36 21.4 39.8 80.0 R_{036-220165 20LPOz10L20-GLL40 1000 10 36 20.9 45.0 90.0} R036-220166 40LPOz10L30-L40 1000 13.3 37 25.0 39.2 78.1 R036-210449 10LPOz10L20-L40 1000 5 36 21.9 42.3 84.9 R036-210460 30LPOz10L20-L40 1000 15 36 22.1 41.7 84.3 * Batch R036-210462 contains 10 wt.% of PEG with molecular weight 1000 g/mol _{** PSD represent particle size distribution of prepared microspheres; Dv,50 means volume average} particle size The particle size distribution (Dv,50 and coefficient of variance (CV)) of the microspheres was measured by laser diffraction as described in Example 8. Ropivacaine content of the microspheres was determined by CHN elemental analysis. In brief, 2.5-5 mg of ropivacaine microspheres, ropivacaine and multiblock copolymer were accurately weighed in a tin foil and combusted at 1150 °C in an Elementar^® Micro Cube with an excess of oxygen to ensure complete sample combustion. The formed N2, CO2, H2O and SO2 gasses were retained by an adsorption column and eluted separately and analysed using a thermal conductivity detector. By comparing the nitrogen content of the ropivacaine microspheres with that of ropivacaine and multiblock copolymer, the ropivacaine content of the ropivacaine microspheres is calculated. The in vitro release of ropivacaine from the microspheres was determined by incubating 10 mg of ropivacaine microspheres in 45 ml in vitro release buffer (100 mM PO4 buffer, 0.025 % Tween-20, 0.02 % NaN3, 290 mOsm/kg, pH 6.5) at 37 °C. At predetermined time points, following centrifugation of the vials, aliquots of 100 ^l release buffer were collected. Ropivacaine concentrations in the release buffer were determined via reversed phase ultra-performance liquid chromatography (UPLC) with UV-detection using a Waters Acquity H-Class UPLC system, equipped with a PDA or UV detector, an Acquity BEH C18 column (50 × 2.1 mm, 1.7 ^m), maintained at 40 °C. Mobile phase A consisted of a 20 mM phosphate buffer pH 6.5 and acetonitrile at a ratio of 90 / 10 v/v and 100 % of acetonitrile was used as mobile phase B. The mobile phase composition started at 30 % B and increased to 70 % B in 2 min, at a constant flow rate of 0.600 ml/min. Detection was performed at 235 nm. 20LP10L20-LL40 has proven to be a great polymer for long-term sustained release of all kinds of drug molecules, including rapamycin (Falke et al., Biomaterials 2015, 42, 151-160, Zandstra et al., Pharm Res.2015, 32(10), 3238-3247), tacrolimus (Sandker et al., ACS Biomater. Sci. Eng.2018, 4(7), 2390–2403) and peptides (WO-A-2013/015685). 20LP10L20-LL40 is a semicrystalline multiblock copolymer. Due to its high melting temperature of 134 °C in combination with a relatively high glass transition temperature of 41 °C 20LP10L20-LL40 allows the development of extended release drug products with excellent stability profile. However, due to use of the crystalline poly(L-lactide) polymer segment, 20LP10L20-LL40 degrades very slowly. It takes about 3-4 years for 20LP10L20-LL40 to degrade completely. Amorphous PEG-containing multiblock copolymers covered by WO-A-2005/6068533 such as 20LP10L20-L40 or 15GP6L12-GL40 are known to provide interesting release kinetics. However, the presence of PEG leads to significant lowering of the Tg of these amorphous multiblock polymers.20LP10L20-L40 has a glass transition temperature of only ~ 30 °C. As a consequence, the long-term storage stability under preferred ambient conditions would be questionable. In order to obtain microspheres with improved storage stability and acceptable polymer degradation rate, an amorphous prepolymer (B) segment composed of poly(glycolide-co-L-lactide) with a glycolide / L-lactide molar ratio of 15 / 85 was chosen. The resulting 20LP10L20-GLL40 multiblock copolymer, with a predicted Tg of 38 °C had a Tg of 34 °C. Ropivacaine-loaded microspheres prepared of 20LP10L20-GLL40 had a ropivacaine loading of 42.7 wt.%, representing an EE of 85.35 %. Figure 3 shows the cumulative in vitro release of ropivacaine from 20LP10L20-GLL40-based microspheres. Release was characterised by a relatively high burst of approximately 20 % at 24 hrs, followed by gradual, close to linear release for 6 weeks. The combination of relatively high initial burst release – which in vivo is typically even higher – and the (still) relatively low Tg of only 34 °C of 20LP10L20-GLL40 – which would make it challenging to obtain drug products with long term shelf-life under ambient storage conditions – initiated exploration of alternative copolymers. To compare the characteristics of POz-based copolymers with PEG-based multiblock copolymers, ropivacaine-loaded MSP were prepared of POz-based copolymers with comparable overall composition (except for the PEG-polymer which was replaced by a POz-block) as the 20LP10L20-GLL40 multiblock copolymer used above. The processability of 20LPOzL20-L40 and 20LPOzL20-GLL40 was comparable. Both polymers exhibited good solubility in DCM and good miscibility with ropivacaine during dissolution. Characterisation of the lyophilised microspheres by scanning electron microscopy showed that the O/W microencapsulation process yielded spherical microspheres with a smooth surface without any pores (Figure 4). The average particle size Dv,50 of the ropivacaine loaded microspheres as analysed by laser diffraction varied between 36 and 39 ^m (Table 10). Ropivacaine content of the microspheres as determined by elemental analysis (Elementar^® Micro Cube) varied between 39 and 45 wt.%, representing encapsulation efficiencies (EE) of 78 to 90 % (Table 10). The ropivacaine-loaded microspheres prepared of POz-based copolymers had similar overall in vitro release kinetics in terms of profile and release duration as microspheres prepared of PEG-based MBCP, except that the burst release of ROP-MSP prepared of POz-based MBCP was significantly lower as compared to ROP-MSP prepared of PEG-based MBCP (Figure 5). Incomplete recovery of ropivacaine from MSP made of 20LPOz10L20-L40 is attributed to the significantly slower degradation of the L40 block which entraps ropivacaine and cause its incomplete release. To further explore the potential of POz-based copolymers ROP-MSP were prepared of a series of other poly(D,L-lactide)-POz1000-poly(D,L-lactide)−b−poly(D,L-lactide)-based copolymers with different block ratio (Table 10). The in vitro release of ROP from ROP-MSP prepared of 10LPOz10L20-L40 was similar in terms of overall release kinetics as compared to MSP prepared of 20LPOz10L20-L40. Surprisingly, the burst release was a bit higher. Unexpectedly, the release of ROP from ROP-MSP prepared of 30LPOz10L20-L40 was extremely fast, which was attributed to the relatively high content (15 wt.%) of water soluble LPOz10L20 block in this copolymer. Apparently, due to high hydrophilicity of this polymer, the cleavage of the lactide ester bonds is that fast that within a very short period, large amounts of prepolymer LPOz10L20 is degraded and dissolved in IVR medium, leading to fast degradation and consequently the release of ropivacaine. By increasing the molecular weight of the POz1000 containing block to 3000, thereby lowering the POz fraction of the hydrophilic block making it insoluble in water, the release of ropivacaine could be slowed down, even though the overall POz1000 content of the resulting 40LPOz10L30-L40 MBCP (13.3 wt.%) was similar to that of 30LPOz10L20-L40. Example 10 In this example, POz-based copolymers were used to prepare levonorgestrel (LNG) loaded implants.1 mm diameter implants with a target LNG loading of 50 wt.% were prepared at a scale of 7 g by hot melt extrusion. In brief, both polymer and LNG were weighed and pre-mixed in a 15 ml vial using a roller bench, after which the powder mixture was fed to a Haake Minilab extruder equipped with a 1-mm cylindrical die, preheated at a process temperature of 120-135 °C. The material was compounded by circulation (open bypass) for 15 min at a screw speed of 15 rpm, after which the bypass was switched-off to extrude the compounded material through the die. The extruded strand was collected on a conveyer and manually cut into implants with a length of around 10 mm. For LNG content analysis, triplicates of 2.0 mg ± 0.3 mg of LNG-loaded implants were dissolved in 3.00 ml of acetonitrile via sonication and heating to 60 °C for 20 min. Dissolved implant samples were diluted with 3.00 ml water and analysed for LNG concentrations using RP-UPLC. Separation was performed on an Acquity™ BEH C18 column (50 × 2.1 mm; 1.7 ^m), maintained at a temperature of 55 °C. Mobile phase consisted of a 50 % acetonitrile in water. Sample run time was 3 min (isocratic), flow rate 0.55 ml/min and the sample injection volume was 3.0 ^l. The column effluent was monitored at a detection wavelength of 243 nm. The recovered contents of LNG were close to the targeted LNG loadings. For in vitro release testing, triplicates of ca.3 mg of LNG containing implants were weighed into a 15.0 ml of IVR buffer (100 mM PO4 buffer, 0.5 % SDS, 0.02 % NaN3, pH 7.4) inside 15 ml tube. Tubes were placed horizontally in a climate chamber at 37 °C ± 1 °C, with shaking at 130 rpm. Tubes were sampled regularly by replacing 14.0 ml of the buffer with 14.0 ml fresh buffer. Samples were analysed using the RP-UPLC method described above and cumulative release curves were constructed from all data points. The list of all prepared LNG containing implant formulations is given in Table 11. Table 11. Characteristics of levonorgestrel loaded implants prepared of several POz-based copolymers Polymer IV Th. LNG EE B_{atch Polymer grade} batch (dl/g) loading % (%) 20LP10L20-GLL40 086A-220353 _{RCP-2208 0.86 52.0 95.8} (15 / 85) 0_{86A-230184 Purasorb PDLG5004 N.A. 0.40 50.2 99.2} 20LPOz10L20-GLL40 113A-220315 _{R031-2201 0.56 50.0 100.8} (15 / 85) 40LPOz10L30-GLL40 113A-220316 _{R031-2211 0.61 50.0 100.7} (15 / 85) 60LPOz10L30-GLL40 086A-230179 _{R031-2303A 0.65 52.1 100.8} (15 / 85) D_{W-2001-72-2 10CPOz10C20-L40 EH-2001-84 0.75 50.0 87.7 DW-2001-72-3 10LPOz10L20-L40 IT-2001-65 0.65 50.0 102.4 DW-2001-72-4 30LPOz10L20-L40 EH-2001-80 0.93 50.0 93.3} Levonorgestrel loaded implants were produced using hot melt extrusion of polymer + LNG blend at high loading of drug (ca.50 wt.%). First round of experiments was performed using POz-based copolymers with L40 block. The non-optimised conditions during extrusion regarding temperature and relatively high IV of used polymers gave highly rough implants (Figure 7). Taking this into account, it is difficult to obtain clear correlation between LNG release kinetics and structural properties of used polymers. However, from Figure 8, it can still be concluded that polymer with L40 block released initially slower and have long lag phase compared to GLL40 polymers that demonstrate close to linear release. GLL40 polymers (both POz and PEG based) were prepared at slightly higher temperatures which resulted in compact implants with a smooth surface (Figure 7). The in vitro release characteristics of LNG implants prepared of POz-based copolymers were compared with the characteristics of LNG implants prepared of PEG based analogues and PLGA polymers (Figure 9). The LNG loaded implants prepared of POz-based copolymers (20LPOz10L20-GLL40) had the same release profile as implants prepared of the PEG-based 20LP10L20-GLL40. However, the Tg of the POz-based multiblock copolymer is 15 °C higher as compared to the Tg of its PEG based analogue polymer which is highly beneficial for storage stability of drug products composed of these materials. All POz-based copolymers demonstrated close to constant release of LNG. In contrast, standard poly(D,L-lactide-co-glycolide) (PLGA) PDLG 5004 exhibit release behaviour typical for PLGA polymers with a long lag phase after the initial burst release followed by degradation induced accelerated drug release. Similar behaviour was obtained for other PLGA polymers where duration of lag phase was determined by the lactide / glycolide monomer ratio of the copolymer. Even though the shape of release curves for 60LPOZ10L30-GLL40 and PDLG 5004 were different, degradation times of both polymers were quite similar. Both polymers were fully degraded after 4.5 months, as shown in Figure 11. It is concluded that the newly developed POz based multiblock copolymers allow more constant release kinetics, allow easy tuning drug release duration while providing short degradation times (preventing polymer accumulation upon repeated administration) as compared to standard PLGA copolymers. Interestingly, LNG implants prepared of 40LPOz10L30-GLL40 exhibited similar cumulative release kinetics as LNG implants prepared of 20LPOz10L30-GLL40. Possible reason for this behaviour might lay in fact that the release of LNG is mostly governed by the diffusion and dissolution of LNG through percolated network of LNG particles. Thus, small changes in POz content do not provide significant difference in release rate. In addition, presence of hydrophobic LNG particles can reduce water uptake of implants and prolong degradation of polymer matrix. Nevertheless, further increasing the POz content from 13.3 wt.% (40LPOz10L30-GLL40) to 20 wt.% (60LPOz10L30-GLL40) resulted in significantly faster release of LNG. The used polymer 60LPOz10L30-GLL40 has a Tg of 51 °C which allows development of solid implants with excellent shelf life during drug product storage. Contrary to this POz containing copolymer, the PEG based analogue (60LP10L30-GLL40) has a Tg of 15 °C (see Example 7), due to which the which any drug products prepared thereof cannot be stored under ambient conditions and most probably cannot be stored under refrigerated conditions either. Instead, drug products prepared of such low Tg polymer most likely need to be stored under frozen conditions (-20 ºC). Example 11 Cylindrical LNG-loaded strands with a target LNG loading of 50 wt.% and diameter of approximately 1.0 mm were manufactured under clean conditions by hot melt extrusion according to the procedure described in Example 10 using 40LPOZ10L30-GLL40 (G / LL = 15 / 85), and a PLGA polymer with a 50 : 50 D,L-lactide : glycolide molar ratio and an intrinsic viscosity of 0.5 dl/g (Expansorb DLG50-5E, Sequens, France) as polymer matrix. Extruded strands were cut to the desired length as to obtain LNG implants with an LNG dose of approximately 6.3 mg (Table 12).

Table 12. Characteristics of levonorgestrel loaded implants evaluated for their in vivo pharmacokinetics in rats. LNG Average Average Average G_{roup Polymer grade} loading length weight LNG (wt.%) (mm) (mg) dose (mg) 40LPOz10L30-GLL40 12.58 ± 6.32 ± 1 50.5 12.6 (G / LL = 15 / 85) 0.13 0.09 12.61 ± 6.31 ± 2 PLGA 50 : 50 IV 0.5 dl/g 50.1 12.6 0.20 0.10 The LNG implants were evaluated for their in vivo pharmacokinetics in adult female (Sprague Dawley) rats of 225-275 g body weight (6 rats per group). LNG implants were inserted subcutaneously in the back of the rats through an incision, with the use of a 14G trocar. The incision was then closed with 1 surgical staple. At predetermined time points, blood samples were collected from the tail vein and evaluated for levonorgestrel concentration by LC-MS. Figure 10 shows the levonorgestrel serum concentrations in rats following the subcutaneous injection of LNG implants composed of 40LPOZ10L30-GLL40 (G / LL = 15 / 85) and PLGA DLG50-5E. Following administration of the implants, the average LNG serum concentrations increased to around 650 pg/ml for all implants, whereafter relatively constant serum concentrations were obtained for the 40LPOZ10L30-GLL40 (G / LL = 15 / 85) based LNG implants. In contrast, PLGA DLG50-5E-based LNG implants showed less constant serum concentrations of LNG with a significant increase in serum LNG concentrations after 3 weeks, which is attributed to acceleration of the degradation of the PLGA polymer. Example 12 In this example, POz-based copolymers synthesised as described in Example 1 were used to prepare ropivacaine loaded in situ forming implants. Ropivacaine-loaded in situ forming implant formulations with a ropivacaine loading of 2 wt.% were prepared using different POz-based copolymers by dissolving ropivacaine base in polymer solution in NMP (polymer : solvent : ropivacaine weight ratio 35 : 63 : 2). Ropivacaine content of the ISFI was determined by RP-UPLC. Approximately 100 mg of ISFI formulation was dissolved in 2 ml of DCM. Subsequently, 10 ml of 1 % acetic acid solution was added to precipitate polymer and extract ropivacaine. After leaving sample on roller mixer for 30 min, sample was centrifuged and supernatant was analysed using RP-UPLC. Ropivacaine containing POz-based depots were formed in situ by slowly adding 45 ml of buffer (100 mM PO4 buffer, 0.025 % Tween^® 20, 0.02 % NaN3, 290 mOsm/kg, pH 6.5, 37 °C) to 100 ^l of the liquid ropivacaine / polymer / NMP formulations. The in vitro release of ropivacaine from the in situ forming implants was determined by collecting aliquots of 100 ^l release buffer at predetermined time points. Ropivacaine concentrations in the release buffer were determined via reversed phase ultra-performance liquid chromatography (UPLC) with UV detection using a Waters Acquity H-Class UPLC system, equipped with a PDA or UV detector, an Acquity BEH C18 column (50 × 2.1 mm, 1.7 ^m), maintained at 40 °C. Mobile phase A consisted of a 20 mM phosphate buffer pH 6.5 and acetonitrile at a ratio of 90 / 10 v/v and 100 % of acetonitrile was used as mobile phase B. The mobile phase composition started at 30 % B and increased to 70 % B in 2 min, at a constant flow rate of 0.600 ml/min. Detection was performed at 235 nm. Table 13 lists all prepared ropivacaine containing in situ forming implant formulations. All formulations demonstrated fast depot formation upon injection in aqueous medium. The viscosity of the solutions was measured by cone-and-plate rotational rheology using an AR2000ex rotational rheometer (TA Instruments, New Castle, DE, USA) with a 40 mm cone, an angle of 1° and a Peltier plate. The gap between cone and plate was 29 ^m. Samples of ca.300 ^l were equilibrated at 25 °C for 180 s after which a 300 s time sweep was initiated, during which the samples were sheared at a shear rate of 5 s^-1. The viscosity of formulations is barely impacted by the addition of ropivacaine or by the composition of the POz polymer, but was significantly affected by the molecular weight (intrinsic viscosity) of the polymers. The only difference in viscosity was observed when comparing 20LPOz6L12-L20 and 20CPOz6C12-L20 polymers (polymers have the same intrinsic viscosity), where the lower viscosity of the 20CPOz6C12-L20 polymer (0.79 Pa∙s) as compared to20LPOz6L12-L20 (0.93 Pa∙s) is attributed to the higher solubility of CPOz6C12 blocks in NMP.

Table 13. Characteristics of ropivacaine in situ forming implants prepared of several POz-based copolymers Viscosity of Viscosity of Polymer IV Wt.% Wt.% Wt.% EE Batch Polymer grade polymer solution formulation batch (dl/g) polymer NMP ropivacaine* (%) (Pa∙s) (Pa∙s)** R038-220270 10LP6L12-L20 RCP-2119 0.31 35 63 2 0.44 0.43 94.9 R038-220271 20LP6L12-L20 RCP-2125 0.33 35 63 2 0.45 0.54 95.6 R038-220272 10LPOz6L12-L20 IT-2001-109 0.32 35 63 2 0.50 0.55 95.5 R038-220273 20LPOz6L12-L20 RCP-2135 0.39 35 63 2 0.93 1.09 95.1 R038-220413 10CPOz6C12-L20 R031-2213 0.38 35 63 2 0.78 0.71 91.5 R038-220414 20CPOz6C12-L20 R031-2212 0.39 35 63 2 0.79 0.85 96.2 R038-220275 PDLG 5004 MS1948-2 0.4 35 63 2 3.91 3.50 92.3 R038-220310 PDLG 7502 MS1986-3 0.2 35 63 2 0.24 0.22 97.2 * Polymer solution contains polymer dissolved in NMP ** Formulation contains polymer and ropivacaine dissolved in NMP

To compare the characteristics of POz-based copolymers with PLGA copolymers that are used as ‘standard’ polymers for preparation of in situ forming implant formulations, ropivacaine-loaded ISFI were prepared using POz-based copolymers together with two mostly used PLGA grades (Table 13 and Figure 12). The ropivacaine loaded in situ forming implant formulations prepared of POz-based copolymers had similar in vitro release duration compared to the selected PLGA polymers. However, the release profile was significantly different. While PLGA polymers in both cases demonstrated initial burst followed by the leg phase in the release, the release profiles of POz-based copolymers were close to linear. In addition, the initial burst was significantly lower for POz-based copolymers compared to the polymer of similar intrinsic viscosity (PLGA5004). The composition of POz-based multiblock copolymers can be used as a tuning parameter for adjustment of release duration. POz-based copolymers with higher POz content exhibited faster ropivacaine release, as higher content of POz leads to higher water uptake and faster degradation of polymer matrix. The clear effect of replacement of PEG segments by POz polymer segments on the release characteristics of in situ forming implant formulations can be observed from Figure 13. Both polymer families demonstrate comparable release duration of ropivacaine. Nevertheless, the shape of release profiles demonstrates some clear differences. PEG-based multiblock copolymers demonstrated higher initial burst release compared to POz-based multiblock copolymers. This difference is even more pronounced at higher content of hydrophilic block. In addition, 20LP6L12-L20 exhibit diffusion-controlled (first order) release profile, while close to linear release (zero-order) is observed with POz-based analogues. The poly(D,L-lactide)−b−POz−b−poly(D,L-lactide) blocks are known to degrade relatively fast. Therefore, in order to explore the possibility to further extend the release duration of ropivacaine, POz-based copolymers composed of a poly(^-caprolactone)−b−POz−b−poly(^-caprolactone) block were evaluated and compared to POz-based copolymers composed of poly(D,L-lactide)−b−POz−b−poly(D,L-lactide) blocks (Figure 14). As expected, the duration of ropivacaine release can be extended by using slower degrading poly(^-caprolactone) blocks in the prepolymer (A) segment to replace the faster degrading poly(D,L-lactide). However, the initial burst release was higher for multiblock copolymers prepared of poly(^-caprolactone) containing POz-based prepolymer (A) segments. This can be explained by the lower affinity of poly(^-caprolactone) containing polymers towards aqueous medium. Replacement of more hydrophilic poly(D,L-lactide) blocks with poly(^-caprolactone) leads to faster solvent exchange and polymer precipitation and thus faster expulsion of ropivacaine. Example 13 In this example, POz-based copolymers synthesised as described in Example 1 were used to prepare leuprolide acetate (LA) loaded in situ forming implants. Leuprolide acetate-loaded in situ forming implant formulations with theoretical loading of 3 wt.% were 5 prepared using different POz-based copolymers by dispersing leuprolide acetate lyophilised powder using spatula in polymer solution in NMP. The results are shown in Table 14. Table 14. Leuprolide acetate containing in situ forming implant formulations prepared using POz-based copolymer Viscosity of Polymer IV Wt.% Wt.% Wt.% Batch Polymer grade polymer solution batch (dl/g) polymer solvent API (Pa∙s) R038-220443 10LPOz6L12-L20 IT-2001-109 0.32 30 67 3 0.50 R038-220525 20LPOz6L12-L20 RCP-2135 0.39 30 67 3 0.93 R038-220444 10CPOz6C12-L20 R031-2213 0.38 30 67 3 0.34 R038-220526 20CPOz6C12-L20 R031-2212 0.39 30 67 3 0.39 R038-220523 10CPOz6C12-L20 R031-2213 0.38 25 72 3 0.17 R038-220524 10CPOz6C12-L20 R031-2213 0.38 20 77 3 0.08 In vitro release (IVR) of LA from ISFI (100 mg) was analysed in triplicates at0 37 °C in 2.0 ml 100 mM PO4 buffer (pH 7.4, 290 mOsm/kg), supplemented with 0.025 % Tween^® 20 and 0.02 % NaN3. At different time points, 1.4 ml of IVR buffer was removed and stored at 2-8 °C until analysis. Subsequently, 1.4 ml of fresh IVR buffer was added to the samples, and the samples were placed back in the climate chamber. Analysis of collected IVR samples for LA was performed by UPLC (see more details on Table 15).5 Table 15. UPLC settings for analysis of LA IVR samples Parameter Setting Waters Acquity UPLC CSH-C18, 50 cm × 2.1 mm; 1.7 ^m Column at 45 °C Mobile phase A 37 mM ammonium acetate buffer pH 9.5 Mobile phase B Water : acetonitrile : TFA (90 : 10 : 0.1, v/v/v) Mobile phase C Water : acetonitrile (90 ; 10, v/v) Mobile phase D 100 % acetonitrile Flow 0.750 ml/min Injection volume 2.0 ^l Detector FLR: ^ ex / em = 280 / 345 nm All prepared formulations demonstrated fast depot formation upon injection in aqueous medium. To compare the characteristics of POz-based copolymers with standard PLGA copolymers used in existing marketed in situ forming implant-based drug products, leuprolide acetate-loaded ISFI were prepared of POz-based copolymers and compared with PLGA7502 polymer-based Eligard 22.5 mg leuprolide acetate for injectable suspension (Tolmar) (Figure 15). The leuprolide acetate loaded in situ forming implant formulations prepared of POz-based copolymers had similar in vitro release duration compared to the selected Eligard 22.5 mg leuprolide acetate ISFI formulation. However, all POz-based batches had different release profile. All POz-based formulations demonstrated significantly lower initial burst release compared to Eligard 22.5 mg leuprolide acetate ISFI formulation. Some of the formulations demonstrated close to linear leuprolide. This all demonstrates the advantages of the new POz-based copolymers as compared to the existing polymers used in current ISFI-based drug products. The change in composition of POz-based copolymers surprisingly did not lead to the significant difference in release duration. However, an increase in POz content in both xxCPOz6C12-L20 and xxLPOz6L12-L20 lead to the increase of the initial burst release. The diffusion of the drug in the second phase of the release was also slightly faster for polymer with higher POz content. Finally, the onset of degradation for the tested polymers is apparently not significantly different, thus leading to similar release duration. In order to get faster or slower release compared to investigated polymers, chemical change in both blocks has to be made. Faster release can be achieved by adding small amount of glycolide in the structure of L20 block, while slower release can be achieved using CPOzC blocks with higher poly(^-caprolactone) content, or adding ^-caprolactone units to the L20 block. Furthermore, release kinetics can be adjusted by adding hydrophobic solvents, such as triacetin and benzyl benzoate. Figure 15 demonstrates that the formulation containing 30 % of 10CPOz6C12-L20 has a long lag phase that is improper for making product that requires constant release. To solve this problem, the concentration of polymer solution was reduced, while keeping the content of drug unchanged (Figure 16). A reduction of polymer concentration of polymer lead to an increase of initial burst. However, the burst increase was more prominent when reducing concentration to 20 %. Formulation with 25 % of polymer demonstrated no lag phase but constant release of leuprolide acetate with release duration similar as formulation with 30 % of polymer. Interestingly, the overall release duration was unaffected by the initial polymer concentration. Example 14 In this example, POz-based copolymers synthesised as described in Example 5 were used to prepare bovine serum albumin (BSA) loaded microspheres (MSP). BSA-loaded microspheres (BSA-MSP) with a target loading of 4.5-5 wt.% were prepared via water-in-oil-in-water (W/O/W) membrane emulsification followed by solvent extraction/evaporation.1.5 g of polymer was dissolved in 8.5 g of dichloromethane (15.0 wt.%) and filtered over a 0.2 ^m PTFE filter. Approximately 0.9 ml aqueous protein solution (170 mg/ml) was added followed by emulsification using a rotor-stator mixer at 25000 rpm for 60 s to yield a primary emulsion. The primary emulsion was then emulsified in 1500 ml of ultrapure water containing 0.4 wt.% PVA and 5 wt.% of NaCl by membrane emulsification using a membrane with 20 ^m pores) to form a secondary emulsion. The secondary emulsion was stirred for 4 h at room temperature to remove dichloromethane by solvent extraction/ evaporation. The resulting microspheres were collected on a 5 ^m membrane filter and washed three times with aqueous 0.05 w/v% Tween^® 80 solution and three times with ultrapure water, after which the hardened microspheres were dried by lyophilisation. The surface morphology of the MSP was examined with SEM using a Jeol Neoscope. The sample was first placed in a carbon conductive tape and subsequently coated with a thin gold layer (3 min coating time). The sample was then introduced to the microscope, a vacuum was applied, and the microspheres were imaged using a 5-10 kV electron beam. The particle size distribution of the MSPs was determined using a Horiba LA-960 Laser Diffraction Particle Analyzer. In brief, MSPs were redispersed in the dispersion medium (demi water). Then, MSP suspension was added to a measuring cell, and a stirring magnet was used to disperse the particles. Two light sources are used in the system, one laser with a wavelength of 650 nm and one LED with 405 nm. The scattering pattern of particles in the solution was determined. Then the size distribution of the particles (a range of 10 nm – 5000 ^m) was calculated based on the Mie Scattering theory. The BSA content of BSA-MSPs was determined in triplicates by BCA Protein Assay after hydrolysis of BSA-MSP by NaOH. Briefly, 10 mg of BSA-MSP was dissolved in 1 ml of DMSO at 80 °C. Then, 5.00 ml of 0.5 % SDS in 0.05 M NaOH was added. The mixture was stirred overnight on a roller mixer at room temperature. Then, 100 ^l of sample was added to the BCA reagent followed by incubation at 60 °C for 10 min. The absorbance was measured at 562 nm. Calibration curve from absorption of standards against absolute amount of BSA in standards was constructed, and BSA amount in samples was calculated by interpolation on calibration curve. In vitro release (IVR) studies with BSA-MSP were conducted in triplicate in 2 ml of 100 mM phosphate buffer (pH 7.4 containing 0.02 w/v% NaN3) thermostated at 37 °C. Samples taken at predetermined time points until completion of release were analysed with RP-UPLC to establish the cumulative protein release against sampling time. The list of prepared microspheres is given in Table 16. All POz-based BSA-MSP had BSA loadings around 5 % corresponding to high encapsulation efficiency of ≈ 100 %. In addition, all prepared microspheres had a smooth surface morphology without pores (Figure 17, Table 16). Table 16. List of prepared BSA-loaded MSP based on POz copolymers POz PSD (µm) * BSA POz Mw EE Batch # POz-MBCP grade content content (g/mol) Dv,50 COV(%) (%) (wt.%) (wt.%) IC075-210439 10LPOz10L20-L40 1000 5.0 30.6 20.4 5.4 107.7 IC075-210535 20LPOz10L20-L40 1000 10.0 31.3 22.6 5.9 123.5 IC075-210309 30LPOz10L20-L40 1000 15.0 34.9 23.3 4.5 90.5 R036-220295 30LPOz10L30-L40 1000 10.0 33.6 20.9 5.0 109.2 R036-220108 40LPOz10L30-L40 1000 13.3 33.1 21.2 4.3 121.0 R036-220296 50LPOz10L30-L40 2000 16.5 33.8 21.6 5.0 116.0 R036-220297 20LPOz20L50-L40 2000 8.0 31.4 21.9 5.0 112.7 R036-220298 30LPOz20L50-L40 2000 12.0 32.6 21.0 5.0 113.2 _{* PSD represent particle size distribution of prepared microspheres} The initial testing with POz-based copolymers (Figure 18) demonstrated. For BSA-MSP prepared of 10LPOz10L20-L40 and 20LPOz10L20-L40 polymers less than 10 % BSA release up to 40 days. Surprisingly, BSA-MSP prepared of 30LPOz10L20-L40 showed very fast release with all BSA completely released within 3 days. This is caused by complete cleavage of the LPOz10L block from the multiblock copolymers within only few days, as could be concluded from¹H-NMR. Due to its high aqueous solubility, the LPOz10L block leaves the polymer matrix quickly thereby causing BSA to be released in parallel as well. To slow down the release of BSA, the POz content of the hydrophilic prepolymer (A) segment was decreased by increasing the poly(D,L-lactide) chain length in the prepolymer (A) segments (Figure 19). As expected, 30LPOz10L30-L40 with longer poly(D,L-lactide) chain length showed significantly slower and more extended release of BSA (sustained release of BSA up to 40 days) than BSA-MSP prepared of 30LPOz10L20-L40. Further increasing the POz content in LPOz10L30 polymers, namely 40LPOz10L30-L40 and 50LPOz10L30-L40 resulted in faster release rates without a lag phase, due to increased swelling degree of polymer. To prevent the lag phase in polymers like 30LPOz10L30-L40, POz-based copolymers with higher POz molecular weight (2000) were used. When using 20LPOz20L50-L40 and 30LPOz20L50-L40 multiblock copolymers, BSA release was sustained up to approximately 50 days without a lag phase (Figure 19). Example 15 In this example, POz-based copolymers synthesised as described in Example 5 were used to prepare antibody loaded microspheres. Immunoglobulin G (IgG) was used as a model antibody. IgG loaded microspheres (IgG-MSP) with a target loading of 4.5-5 wt.% were prepared via water-in-oil-in-water (W/O/W) membrane emulsification followed by solvent extraction/evaporation.1.5 g of polymer was dissolved in 8.5 g of dichloromethane (15.0 wt.%) and filtered over a 0.2 ^m PTFE filter. Approximately 1 ml aqueous antibody solution (75 mg/ml) was added followed by emulsification using a rotor-stator mixer at 21600 rpm for 60 seconds to yield a primary emulsion. The primary emulsion was then emulsified in 1500 ml of ultrapure water containing 0.4 wt.% PVA and 5 wt.% of NaCl by membrane emulsification using a membrane with 20 ^m pores) to form a secondary emulsion. The secondary emulsion was stirred for 4 h at room temperature to remove dichloromethane by solvent extraction/evaporation. The resulting microspheres were collected on a 5 ^m membrane filter and washed three times with aqueous 0.05 w/v% Tween^® 80 solution and three times with ultrapure water, after which the hardened microspheres were dried by lyophilisation. The surface morphology of the IgG-MSP was examined with SEM using a Jeol Neoscope. The sample was first placed in a carbon conductive tape and subsequently coated with a thin gold layer (3 min coating time). The sample was then introduced to the microscope, a vacuum was applied, and the microspheres were imaged using a 5-10 kV electron beam. The particle size distribution of the MSPs was determined using a Horiba LA-960 Laser Diffraction Particle Analyzer. In brief, MSPs were redispersed in the dispersion medium (demi water). Then, MSP suspension was added to a measuring cell, and a stirring magnet was used to disperse the particles. Two light sources are used in the system, one laser with a wavelength of 650 nm and one LED with 405 nm. The scattering pattern of particles in the solution was determined. Then the size distribution of the particles (a range of 10 nm – 5000 ^m) was calculated based on the Mie Scattering theory. Total content of IgG-MSPs was determined in triplicates by BCA Protein Assay after hydrolysis of IgG-MSP by NaOH. Briefly, 10 mg of IgG-MSP was dissolved in 1 ml of DMSO at 80 °C. Then, 5.00 ml of 0.5 % SDS in 0.05 M NaOH was added. The mixture was stirred overnight on a roller mixer at room temperature. Then, 100 ^l of sample was added to the BCA reagent followed by incubation at 60 °C for 10 min. The absorbance was measured at 562 nm. Calibration curve from absorption of standards against absolute amount of IgG in standards was constructed, and IgG amount in samples was calculated by interpolation on calibration curve. In vitro release (IVR) studies with IgG-MSP were conducted in triplicate in 2 ml of 100 mM phosphate buffer (pH 7.4 containing 0.02 w/v% NaN3) thermostated at 37 °C. Samples taken at predetermined time points until completion of release were analysed with SEC-UPLC to establish the cumulative protein release against sampling time. Table 17 lists the prepared IgG-MSP. All POz-based IgG-MSP microspheres demonstrated loading around 5 % which corresponds to complete encapsulation of IgG (100 %). As in case of BSA-MSPs, all prepared microspheres had a smooth surface without any pores (Figure 20, Table 17). Table 17. List of prepared IgG-MSP based on POz copolymers IgG Actual PSD Polymer target Th. IgG EE (Dv,50 Batch# Polymer conc. loading Loading content (%) µm, Wt% (wt.%) (wt.%) COV%) R045-230326 40LPOz10L30-L40 15 5.0 4.6 4.9 106.1 31 (20) R045-230330 30LPOz10L30-L40 15 5.0 4.6 4.8 103.9 32 (21) R045-230331 50LPOz10L30-L40 15 5.0 4.7 4.9 104.5 32 (21) R045-230332 20LPOz20L50-L40 15 5.0 4.7 4.7 102.2 30 (20) R045-230333 30LPOz20L50-L40 15 5.0 4.7 4.8 104.1 31 (20) IVR studies performed with IgG-MSp demonstrated similar release behaviour as obtained for BSA-MSP (Figure 21). Nevertheless, few differences were observed. Unexpectedly, extremely low initial burst was observed for all IgG-MSP formulations. Contrary to BSA, IgG-MSP demonstrated a lag phase for all xxLPOz10L30-L40 polymers. Interestingly, the duration of the lag phase was tuneable by the amount of LPOz10L30 block in the POz copolymer. Contrary to xxLPOz10L30-L40 copolymers, xxLPOz20L50-L40 polymers demonstrated more constant release of IgG, mostly due to higher POz molecular weight that allows faster initial diffusion of IgG. To further test the ability of POz copolymers to encapsulate high amounts of IgG, IgG-MSPs were prepared using 30LPOz20L50-L40 polymer with aimed 10 and 15 % of IgG. Unexpectedly, complete encapsulation of antibody was obtained irrespective of IgG concentration and O / W1 ratio (Table 18). Polymer 30LPOZ20L50-L40 was able to sustain the release of IgG even at as high loadings as 15 wt.% (Figure 22). The initial burst release increased after increasing IgG loading. In addition, higher initial burst was obtained when lower polymer concentration was used for MSP production. Still, the initial release was below 10 % when high polymer concentration was used. The release duration was unaffected by the loading of IgG. The high loading coupled with high encapsulation efficiency and low initial burst with sustained release of IgG makes these polymers excellent candidates for the development of long-acting injectable microsphere formulations for antibodies.

Table 18. Characteristics of IgG-loaded MSPs prepared of POz-based copolymers Polymer IgG PSD (^m)* IgG Targeted IgG O/W1 EE Batch# POz-MBCP grade concentration concentration content content (wt.%) ratio Dv,50 (^m) CV (%) (%) (%) (mg/ml) (wt.%) R045-230461 30LPOz20L50-L40 10.1 15 234 12.0 30.8 20.7 10.7 106.3 R045-230462 30LPOz20L50-L40 10.1 10 177 13.5 29.3 23.6 11.6 115.2 R045-230463 30LPOz20L50-L40 14.7 14 234 8.0 30.1 22.4 17.4 118.8 R045-230464 30LPOz20L50-L40 15.2 10 177 8.5 30.3 19.6 18.2 119.8 * _{PSD represent particle size distribution of prepared microspheres}

Example 16 This example describes the synthesis and characterisation of [poly(D,L-lactide)-co-POz-co-poly(D,L-lactide)]−b−[polyorthoester] and polycaprolactone-co-POZ-co-polycaprolactone]−b−[polyorthoester] multiblock copolymers. First a high Tg poly(orthoester) prepolymer block was synthesised by polyaddition reaction between a diol and an acetal, more specifically from cyclohexane dimethanol (CHDM) and 3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5]undecane (DVTOSU) to obtain a CHDM based poly(ortho ester) prepolymer block, hereafter abbreviated as POE. To obtain a bifunctional POE block, up to 10 wt.% excess of CHDM over DVTOSU was used and the polyaddition reaction was monitored using NMR spectroscopy. The molecular weight of the POE prepolymers was determined using GPC relative to polystyrene standards and NMR spectroscopy with an internal standard. The diol-functionalised CHDM based POE prepolymer had an Mn of ~ 2.6 kg/mol (hereafter abbreviated as ppPOE25) and a Tg of 75 °C. 10LPOZ10L20-POE25 was prepared by chain-extension of ppPOE25 with ppLPOZ10L20 prepolymer with POZ Mn of 1071 g/mol and prepolymer Mn of 2000 g/mol synthesised as described in Example 4 using BDI as a chain extender. After drying of 270.07 g ppPOE25 in a flange glass reactor, a 50 wt.% dioxane solution containing 30.14 g of ppLPOZ10L20 was added and dissolved in distilled p-dioxane to a final concentration of 30 wt.% after which the reaction mixture was heated to 80 °C and 10.59 g of BDI was added. Chain extension, work-up and drying of 10LPOZ10L20-POE25 were performed according to the procedures described in Example 1. Similarly, 10LPOZ6L12-POE25, 40LPOZ10L30-POE25, 20LPOZ20L50-POE25, 20LPOZ30L50-POE25, 10CPOZ6C12-POE25, 20CPOZ10C20-POE25, 10CPOZ20C50-POE25 and 20CPOZ30C50-POE25 were synthesised. Example 17 This example describes the synthesis and characterisation of POz−b−[polyorthoester] multiblock copolymer with a block ratio of 20 / 80 w/w (20POz10-POE25). First a high Tg poly(orthoester) prepolymer block was synthesised as described in Example 16. 20POz10-POE25 was prepared by chain-extension of ppPOE25 with ppPOZ10 prepolymer with Mn of 1071 g/mol synthesised as described in Example 1 using BDI as a chain extender.32.18 g of ppPOE25 and 8.05 g of ppPOZ10 were dried in a flange glass reactor and dissolved in distilled p-dioxane to a final concentration of 20 wt.% after which the reaction mixture was heated to 80 °C and 2.92 g of BDI was added. The polymer was isolated by precipitation in cold ethanol (~ 5 °C) and dried in a vacuum oven at 75 °C yielding dry polymer. The so-obtained 20POz10-POE45 with an intrinsic viscosity of 0.78 dl/g had a first Tg of 57 °C and a second Tg of 100 °C, as determined by modulated differential scanning calorimetry. Using similar procedures, ppPOE25 was chain extended with POZ prepolymers with molecular weights of 600, 1000, 2000 and 3000 in 10 / 90 wt.% ratio and using BDI as a chain extender to yield 10POZ6-POE25, 10POZ10-POE25, 10POZ20-POE25 and 10POZ30-POE25.

Claims

Claims 1. Biodegradable, thermoplastic multiblock copolymer, comprising at least one prepolymer (A) segment and at least one hydrolysable amorphous prepolymer (B) segment, wherein the segments are linked by a multifunctional chain extender, wherein the at least one prepolymer (A) segment comprises: a) a water-soluble polyoxazoline-based polymer, b) one or more hydrolysable linkages, and c) reaction products of one or more cyclic monomers and/or one or more non-cyclic monomers, wherein the water-soluble polyoxazoline-based polymer is a polymer containing a repeating unit of structure −[N(COR¹)CH2CH2]n− where R¹ is independently selected for each repeating unit from an alkyl group and n is 3-100, and wherein the multiblock copolymer is amorphous.

2. Biodegradable thermoplastic multiblock copolymer according to claim 1, wherein the hydrolysable linkages comprise one or more selected from the group consisting of esters linkages, orthoester linkages, carbonate linkages, anhydride linkages, amide linkages, phosphate linkages, phosphazene linkages, urethane linkages, and urea linkages.

3. Biodegradable, thermoplastic multiblock copolymer according to claim 1 or 2, wherein the hydrolysable amorphous prepolymer (A) segment comprises a polymer according to Formula (I) or Formula (II) or a mixture thereof: −X−POz−X− (I) Y−POz−(X−)2 (II), wherein, i_{) POz is the polyoxazoline-based polymer} ii) X are hydrolysable linkages, and iii) Y is an end group originating from the initiator used in the preparation of the polyoxazoline-based polymer

4. Biodegradable, thermoplastic multiblock copolymer according to claim 3, wherein Y is a methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, pentyl, hexyl, allyl, propargyl, 3-butynyl, benzyl, trityl, dodecyl, hexadecyl, or octadecyl group.

5. Biodegradable, thermoplastic multiblock copolymer according to the claim 4, wherein the initiator is selected from group consisting of methyl tosylate, ethyl tosylate, n-propyl tosylate, iso-propyl tosylate, n-butyl tosylate, iso-butyl tosylate, pentyl tosylate, hexyl tosylate, allyl tosylate, propargyl tosylate, 3-butynyl tosylate, methyl triflate, ethyl triflate, n-propyl triflate, iso-propyl triflate, n-butyl triflate, iso-butyl triflate, pentyl triflate, hexyl triflate, allyl triflate, propargyl triflate, 3-butynyl triflate, methyl nosylate, ethyl nosylate, n-propyl nosylate, iso-propyl nosylate, n-butyl nosylate, iso-butyl nosylate, pentyl nosylate, hexyl nosylate, allyl nosylate, propargyl nosylate, 3-butynyl nosylate, methyl iodide, benzyl bromide and trityl bromide.

6. Biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-5, wherein the reaction products of one or more cyclic monomers are selected from the group consisting of lactide (L, D or DL), glycolide, ^-caprolactone, ^-valerolactone, trimethylene carbonate, tetramethylene carbonate, 1,5-dioxepane-2-one, 1,4-dioxane-2-one (p-dioxanone) or cyclic anhydrides (oxepane-2,7-dione).

7. Biodegradable, thermoplastic multiblock copolymer, comprising at least one prepolymer (A) segment and at least one hydrolysable amorphous prepolymer (B) segment, wherein the segments are linked by a multifunctional chain extender, wherein (i) the at least one prepolymer (A) segment comprises a water-soluble polyoxazoline-based polymer, wherein the water-soluble polyoxazoline-based polymer is a polymer containing a repeating unit of structure −[N(COR¹)CH2CH2]n− where R¹ is independently selected for each repeating unit from an alkyl group and n is 3-100, and (ii) the at least one hydrolysable amorphous prepolymer (B) segment comprises the , wherein n is 4-100, such as 5-50; x is 0.25-1 and x + y = 1; p is 0 or 1; R¹ and R² are independently selected from hydrogen and C1-C4 alkyl; Q² is selected from R³ is selected from hydrogen and C1-C6 alkyl, R⁴ is selected from hydrogen and C1-C4 alkyl, and R⁵ v is 1-100, w is 1-12, and R⁶ is selected from hydrogen and C1-C6 alkyl.

8. Biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-7, wherein the water-soluble polyoxazoline-based polymer is present in the at least one prepolymer (A) segment in pendant and/or linear form.

9. Biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-8, wherein the at least one prepolymer (A) segment is selected from the group consisting of poly(D,L-lactide)-co-POz-co-poly(D,L-lactide), poly(glycolide)-co-POz-co-poly(glycolide), poly(ε-caprolactone)-co-POz-co-poly(ε-caprolactone), and poly(p-dioxanone)-co-POz-co-poly(p-dioxanone).

10. Biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-9, wherein the at least one prepolymer (A) segment is selected from the group consisting of [poly(ε-caprolactone-co-D,L-lactide)]-co-POz-co- [poly(ε-caprolactone-co-D,L-lactide)], [poly(ε-caprolactone-co-glycolide)]-co-POz-co-[poly(ε-caprolactone-co-glycolide)], [poly(ε-caprolactone-co-p-dioxanone)]-co-POz-co-[poly(ε-caprolactone-co-p-dioxanone)], [poly(D,L-lactide-co-glycolide)]-co-POz-co-[poly(D,L-lactide-co-glycolide)], [poly(D,L-lactide-co-p-dioxanone)]-co-POz-co-[poly(D,L-lactide-co-p-dioxanone)], and [poly(glycolide-co-p-dioxanone)]-co-POz-co-[poly(glycolide-co-p-dioxanone)].

11. Biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-10, wherein said at least one prepolymer (A) segment comprises a water-soluble polyoxazoline-based polymer.

12. Biodegradable, thermoplastic multiblock copolymer according to claim 11, wherein said water-soluble polyoxazoline-based polymer is derived from 2-substituted-2-oxazoline containing repeating units, more preferably said 2-substituted-2-oxazoline is 2-ethyl-2-oxazoline polymerised via cationic ring-opening polymerization to form a water-soluble poly(2-ethyl-2-oxazoline) polymer having a Mn of 400-10000 g/mol.

13. Biodegradable, thermoplastic multiblock copolymer according to claim 12, wherein said water-soluble poly(2-ethyl-2-oxazoline) polymer has a Mn of 500-5000 g/mol, preferably 600-3000 g/mol.

14. Biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-13, wherein said multifunctional chain extender is a difunctional aliphatic chain extender.

15. Biodegradable, thermoplastic multiblock copolymer according to claim 14, wherein said difunctional aliphatic chain extender is a diisocyanate.

16. Biodegradable, thermoplastic multiblock copolymer according to claim 15, wherein said diisocyanate is 1,4-butane diisocyanate.

17. Biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-16, wherein the at least one hydrolysable amorphous prepolymer (B) segment comprises one or more selected from the group consisting of polyester, polyetherester, polyorthoester, polycarbonate or polyanhydride; or prepolymers of combined ester, orthoester, ether, anhydride and/or carbonate groups thereof.

18. Biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-17, wherein the at least one prepolymer (B) segment is selected from the group consisting of poly(D,L-lactide), poly(D,L-lactide-co-L-lactide), poly(D,L-lactide-co-glycolide), poly(L-lactide-co-glycolide), and a polyorthoester derived from cyclohexane dimethanol and 3,9-divinyl-2,4-8,10-tetraoxaspiro[5.5]undecane.

19. Biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-18, which is amorphous and has at least one glass transition temperature Tg of 10 °C or more, preferably 30 °C or more, more preferably 40 °C or more, such as 40-110°C.

20. Biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-19, wherein the prepolymer (A) segment has a number average molecular weight (Mn) of between 400 and 30000 g/mol, preferably between 500 g/mol and 10000 g/mol, more preferably between 1000 and 8000 g/mol, such as between 1500 and 8000 g/mol, or between 2000 and 7000 g/mol.

21. Biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-20, wherein the prepolymer (B) segment has a number average molecular weight (Mn) of 1000 g/mol or more, preferably between 2000 and 10000 g/mol, or between 3000 and 8000 g/mol.

22. Biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-21, wherein the prepolymer (A) segment is present in an amount of 1-70 % based on total weight of the multiblock copolymer, such as 2-60 %, 3-50 %, 4-45 %, or 5-40 %.

23. Biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-22, wherein the prepolymer (B) segment is present in an amount of 30-99 % based on total weight of the multiblock copolymer, such as 40-98 %, 50-97 %, 55-96 %, or 60-95 %.

24. Biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-23, having an intrinsic viscosity of 0.1 dl/g or more, preferably 0.1-3 dl/g, more preferably 0.2-2 dl/g, such as 0.3-1 dl/g.

25. Biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-24, wherein the prepolymer (A) segments and the prepolymer (B) segments are randomly distributed in the multiblock copolymer.

26. Process for preparing a biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-25, comprising a chain-extension reaction of prepolymer (A) and prepolymer (B) in the presence of a multifunctional chain extender.

27. Pharmaceutical composition for delivery of at least one pharmacologically active compound to a host, comprising at least one pharmacologically active compound encapsulated in a matrix, wherein said matrix comprises at least one biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-25.

28. Pharmaceutical composition according to claim 27, wherein said pharmaceutical composition is in the form of one or more selected from the group consisting of microparticles, microspheres, microgranules, nanoparticles, nanospheres, rods, solid implants, gels, in situ forming implants, coatings, films, sheets, sprays, tubes, membranes, meshes, fibres, and plugs.

29. Pharmaceutical composition according to claim 27 or 28, wherein said pharmaceutical composition is in the form of microparticles, microgranules and/or microspheres.

30. Pharmaceutical composition according to claim 29, wherein the average diameter of the microparticles, microgranules and/or microspheres is in the range of 0.1-1000 µm, preferably in the range of 1-100 µm, more preferably in the range of 10-70 µm.

31. Pharmaceutical composition according to claim 27 or 28, wherein said pharmaceutical composition is in the form of an in situ forming implant, wherein the pharmacologically active compound is dissolved or suspended in a solution of the biodegradable, thermoplastic multiblock copolymer in an acceptable organic solvent such as n-methylpyrrolidone, dimethylsulphoxide, benzyl benzoate, benzyl alcohol, triacetin, glycofurol, polyethylene glycol and which solution, following administration into the body, forms in situ a depot by replacement of the organic solvent by aqueous body fluids thereby entrapping the pharmacologically active compound in the biodegradable, thermoplastic multiblock copolymer depot, from which the pharmacologically active compound is subsequently gradually released.

32. Pharmaceutical composition according to claim 27 or 28, wherein said pharmaceutical composition is in the form of a solid implant prepared by hot-melt extrusion or injection moulding, and wherein the pharmacologically active compound is incorporated in the biodegradable, thermoplastic multiblock copolymer as a molecular blend or as a dispersion of solid particles.

33. Pharmaceutical composition according to any one of claims 27-32, wherein said at least one pharmacologically active compound comprises a small molecule, having a molecular weight of 1000 Da or less, a polypeptide, a polynucleotide, or combinations thereof, in which the polypeptide comprises a peptide, a protein, a monoclonal antibody, or an antibody fragment, and in which the polynucleotide comprises an nucleic acid or an oligonucleotide, such as an antisense oligonucleotide.

34. Pharmaceutical composition in the form of microspheres, microparticles, nanoparticles, nanospheres, rods, solid implants, gels, in situ forming implants, coatings, films, sheets, sprays, tubes, membranes, meshes, fibres, scaffolds or plugs, wherein said medical device comprises a biodegradable, thermoplastic multiblock copolymer according to any one of claims 1-25.

35. Pharmaceutical composition according to claim 34, wherein said dosage form further comprises at least one pharmacologically active compound encapsulated in the matrix of said biodegradable, thermoplastic multiblock copolymer and being released in a controlled way after administration into a human or animal via injection, insertion or implantation.

36. Method of delivering a pharmacologically active compound to a subject in need thereof, comprising administering an effective dose of a pharmaceutical composition according to any one of 27-35 to said subject.