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A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Applied Biosciences and Bioengineering".

Deadline for manuscript submissions: closed (30 December 2023) | Viewed by 15302

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Dr. Antonia Mancuso

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Guest Editor

Department of Experimental and Clinical Medicine, University “Magna Græcia” of Catanzaro, 88100 Catanzaro, Italy
Interests: nanomedicine; nanotechnology; cutaneous diseases; topical and transdermal drug delivery; target therapy

Dr. Gianpiero Calabrese

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Guest Editor

Department of Pharmacy, Kingston University, London KT1 2EE, UK
Interests: drug delivery; polymeric nanoparticles; liposomes and carbon nanotubes for the targeting of the central nervous system; design; synthesis and formulation of boron-containing compounds for selective mitochondrial targeting in the boron neutron capture therapy of brain cancers; electronic cigarettes; analysis of content; public health issues related to pharmacy practice; pharmacology/toxicology; formulation
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Dear Colleagues,

We are pleased to announce a Special Issue titled “Young Investigators in Advanced Drug Delivery”. The Special Issue is a collection of manuscripts focusing on advanced drug delivery systems to improve the therapeutic efficacy of active compounds. Topics of interest include but are not limited to nanomedicine and nanotechnology, innovative drug delivery systems for target therapy, controlled release technology, tissue engineering and regenerative medicine, input on scalable manufacturing protocols, and in vitro and in vivo evidence. This Special Issue aims to highlight the outstanding contributions of young investigators in the field of advanced drug delivery systems. In this context, young researchers are encouraged to submit their latest findings. Review articles summarizing the reality of advanced drug delivery systems and current issues facing the drug delivery field are also welcome.

The only requirement is that at least one young investigator (under 35 years old) is the co-author of the submitted manuscript.

Dr. Antonia Mancuso
Dr. Gianpiero Calabrese
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Applied Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

advanced drug delivery
nanotechnology
characterization studies
target therapy
sustained release
translational medicine
regenerative medicine
drug delivery issues

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Published Papers (7 papers)

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25 pages, 9087 KiB

Open AccessArticle

Computational Design of a Novel Dithranol–Salicylic Acid Antipsoriatic Prodrug for Esterase-Activated Topical Drug Delivery

by Natália Andrýsková, Jozef Motyčka, Melánia Babincová, Peter Babinec and Mária Šimaljaková

Appl. Sci. 2024, 14(3), 1094; https://doi.org/10.3390/app14031094 - 27 Jan 2024

Viewed by 1129

Abstract

Psoriasis is a chronic autoimmune skin disorder characterized by the rapid overproduction of skin cells, resulting in the formation of red, inflamed, and scaly patches or plaques on the skin. Dithranol, also known as anthralin, is a very effective topical medication used in the treatment of psoriasis, with several shortcomings like photo-instability; staining skin, clothing, and bedding; and causing skin irritation. Antiproliferative dithranol is frequently used in combination therapy with keratolytic salicylic acid. We have therefore proposed a novel topical antipsoriatic prodrug comprising dithranol and salicylic acid joined together with an ester bond, specifically 8-hydroxy-9-oxo-9,10-dihydroanthracen-1-yl-2-hydroxybenzoate. An ester bond is cleavable by endogenous esterase hydrolyzing this bond and releasing dithranol and salicylic acid in a 1:1 stoichiometric ratio. We performed an exhaustive theoretical analysis of this molecule using the reliable computational methods of quantum chemistry and ADME in silico studies to investigate its biological and pharmacokinetic activities. We found its molecular structure, vibrational spectra, molecular orbitals, MEP (molecular electric potential), UV-VIS spectra, and TDOS (total density of states), and we performed an RDG (reduced density gradient) analysis. The obtained results may be useful for the understanding of its properties, which may assist in the synthesis and further experimental study of this possible antipsoriatic dual-action prodrug with reduced adverse effects and enhanced therapeutic efficacy. Full article

(This article belongs to the Special Issue Young Investigators in Advanced Drug Delivery)

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0 pages, 8921 KiB

Open AccessArticle

Biocompatible Fe-Based Metal-Organic Frameworks as Diclofenac Sodium Delivery Systems for Migraine Treatment

by Aleksandra Galarda and Joanna Goscianska

Appl. Sci. 2023, 13(23), 12960; https://doi.org/10.3390/app132312960 - 4 Dec 2023

Cited by 1 | Viewed by 1404

Abstract

Migraine is now the sixth most common disease in the world and affects approximately 15% of the population. Non-steroidal anti-inflammatory drugs, including ketoprofen, diclofenac sodium, and ibuprofen, are often used during migraine attacks. Unfortunately, their efficiency can be reduced due to poor water solubility and low cellular uptake. This requires the design of appropriate porous carriers, which enable drugs to reach the target site, increase their dissolution and stability, and contribute to a time-dependent specific release mode. In this research, the potential of the MIL-88A metal-organic frameworks with divergent morphologies as diclofenac sodium delivery platforms was demonstrated. Materials were synthesized under different conditions (temperature: 70 and 120 °C; solvent: distilled water or N,N-Dimethylformamide) and characterized using X-ray diffraction, low-temperature nitrogen adsorption/desorption, thermogravimetric analysis, infrared spectroscopy, and scanning electron microscopy. They showed spherical, rod- or diamond-like morphologies influenced by preparation factors. Depending on physicochemical properties, the MIL-88A samples exhibited various sorption capacities toward diclofenac sodium (833–2021 mg/g). Drug adsorption onto the surface of MIL-88A materials primarily relied on the formation of hydrogen bonds, metal coordination, and electrostatic interactions. An in vitro drug release experiment performed at pH 6.8 revealed that diclofenac sodium diffused to phosphate buffer in a controlled manner. The MIL-88A carriers provide a high percentage release of drug in the range of 58–97% after 24 h. Full article

(This article belongs to the Special Issue Young Investigators in Advanced Drug Delivery)

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10 pages, 2171 KiB

Open AccessArticle

Raman Spectroscopy to Monitor the Delivery of a Nano-Formulation of Vismodegib in the Skin

by Gisela Eliane Gómez, María Natalia Calienni, Silvia del Valle Alonso, Fernando Carlos Alvira and Jorge Montanari

Appl. Sci. 2023, 13(13), 7687; https://doi.org/10.3390/app13137687 - 29 Jun 2023

Cited by 4 | Viewed by 1318

Abstract

Raman spectroscopy was used to detect low quantities of Vismodegib in the skin after its topical application via transfersomes. Vismodegib is a novel antineoplastic drug approved for oral administration for treatment of basal cell carcinoma. Transfersomes loaded with Vismodegib were prepared by thin film resuspension and extrusion, and were characterized physicochemically. Transfersomes were applied to human and pig skin specimens using the Saarbrücken penetration model. The skin was then sectioned by tape stripping, followed by penetration assessment by UV-Vis spectroscopy and Raman spectroscopy in a confocal Raman microscope. Raman signals from Vismodegib and transfersomes were recovered from skin sections, showing a similar distribution in the stratum corneum obtained by the other techniques. On the other hand, pig and human skin showed differences in their penetration profiles, proving their lack of equivalence for assessing the performance of these transfersomes. Raman spectroscopy appears as a potential non-invasive, direct tool for monitoring hard-to-detect molecules in a complex environment such as the skin. Full article

(This article belongs to the Special Issue Young Investigators in Advanced Drug Delivery)

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Figure 1

Figure 1
Laurdan excitation and emission GP spectra of empty transfersomes (T) and VDG-loaded transfersomes (T + VDG) at 25 °C. The curves consist of the averages of three independent measurements. Full article ">Figure 2
VDG recovered from the different sections of human and pig skin incubated with same amounts of T + VDG for 1 h at 35 °C (n = 4). VDG was expressed as the percentage recovered from skin relative to the initial concentration of the incubated drug. Data are shown as mean ± SD. Full article ">Figure 3
Raman spectra of tapes from tape stripping. In the upper part, the results from human skin samples are shown, while the lower part corresponds to pig skin samples. The controls were tapes stripped from untreated skin samples. Arrows show the peaks found corresponding to the VDG Raman signal. Full article ">Figure 4
Raman spectra of VED from the remaining skin after tape stripping. The upper part shows the results from human skin samples, while the lower part corresponds to pig skin samples. In both cases, empty transfersomes (T) and VDG-loaded transfersomes (T + VDG) are shown. Arrows show the peaks found corresponding to the Raman signal of VDG, or from the lipid matrix of the transfersomes (T). Full article ">Figure 5
Enlarged version of the Raman spectra for T and T + VDG in VED of human skin in the region ranging from 600 to 800 cm−1 and their fourth derivatives (in short dash), showing a slight shoulder at 770 cm−1 attributable to the VDG signal. Full article ">

14 pages, 3287 KiB

Open AccessArticle

Incorporation of UV Filters into Oil-in-Water Emulsions—Release and Permeability Characteristics

by Anna Olejnik and Joanna Goscianska

Appl. Sci. 2023, 13(13), 7674; https://doi.org/10.3390/app13137674 - 28 Jun 2023

Cited by 4 | Viewed by 1668

Abstract

Unlike in many countries, in the USA, UV filters are treated as drugs and strictly regulated by the Food and Drug Administration. So far, 17 physical and chemical sunscreen agents were approved there to protect against the harmful effects of UV irradiation. In the European Union, access to UV filters is much larger, which gives manufacturers more options to create new sunscreen products in the form of lotions, sprays, oils, creams, gels, pastes, and sticks. Recently, concerns have been raised about the potential unfavorable effects of some UV filters that can penetrate the skin and enter into the systematic circulation. In this study, we prepared oil-in-water emulsions containing two commonly applied sunscreen agents, avobenzone and octyl methoxycinnamate. The formulations were characterized by a high stability at room temperature and a pH in the range of 6.02–6.11. The processes of sunscreen agent release and permeation were performed in a receptor fluid with a pH 5.8 using Strat-M and cellulose membranes to mimic the skin. It was proved that octyl methoxycinnamate exhibited different liberation and permeation patterns than avobenzone, mostly due to its higher lipophilicity. Both processes were also influenced by the type of membrane applied. The liberation of UV filters to the receptor fluid via the cellulose membrane depended on their concentration in the emulsion. As the amount of sunscreen agent in the formulation increases, more of its molecules diffuse to the receiving medium after 48 h. The permeation of the UV filters through the Strat-M membrane occurs at a very low level, 2% for octyl methoxycinnamate and 0.3% for avobenzone, which supports the safety and efficacy of the topical formulations obtained. Full article

(This article belongs to the Special Issue Young Investigators in Advanced Drug Delivery)

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Graphical abstract
Full article ">Figure 1
Transmission and backscattering profiles of emulsions without UV filter (A) and with avobenzone E0.5%Avo (B), E2%Avo (C), and octyl methoxycinnamate E2%OMC (D). Full article ">Figure 2
Changes in the stability index of formulations obtained. Full article ">Figure 3
Particle size distributions of topical formulations measured without (A) and with the use of ultrasounds (B). Full article ">Figure 4
Optical microscope images of emulsions without (A) and with sunscreen agents: E0.5%Avo (B), E2%Avo (C), E0.5%OMC (D), E2%OMC (E). Full article ">Figure 5
UV spectra of avobenzone and octyl methoxycinnamate in receptor fluid (mixture of ethanol and phosphate buffer of pH 5.8). Full article ">Figure 6
The release profile of avobenzone and octyl methoxycinnamate from emulsions through the cellulose membrane (A), and cumulative amount of UV filters permeated through the Strat-M membrane (B). Full article ">

12 pages, 2737 KiB

Open AccessArticle

Optimal Preparation Protocol of Cell-Encapsulating Alginate Capsules for Long-Term Cell-Based Therapy

by Ryota Suzuki, Kosuke Kusamori, Kodai Takamura, Yuma Miyakawa, Shu Obana, Shoko Itakura and Makiya Nishikawa

Appl. Sci. 2023, 13(11), 6676; https://doi.org/10.3390/app13116676 - 30 May 2023

Cited by 1 | Viewed by 2368

Abstract

Cell-based therapy is an excellent therapeutic modality that involves cell transplantation into patients; however, given that most transplanted cells die immediately post-transplantation, the application of this strategy remains limited. Cell encapsulation is a promising technique for prolonging the survival of transplanted cells, although a definitive encapsulation protocol is yet to be established. Herein, we selected sodium alginate as a polymer for cell encapsulation and optimized the structure and function of cell-encapsulating alginate capsules. First, alginate capsules were prepared using various concentrations of sodium alginate and calcium chloride solution. The NanoLuc luciferase (Nluc)-expressing murine mesenchymal stem cell line C3H10T1/2 was used to prepare the alginate capsules, and cell survival was evaluated after transplantation into mice. The structural properties of the alginate capsules were dependent on the preparation conditions. Capsules with adequate hardness were obtained using 1% sodium alginate and 10% calcium chloride solutions. Alginate capsules encapsulating 5 × 10³ C3H10T1/2/Nluc cells/10 μL maintained a constant cell number over time under in vitro culture conditions. After transplantation into mice, C3H10T1/2/Nluc cells encapsulated in alginate capsules exhibited a significantly longer survival (≥40 days) than suspended cells. Based on these findings, cell-encapsulating alginate capsules with optimal properties can be used for long-term cell-based therapies. Full article

(This article belongs to the Special Issue Young Investigators in Advanced Drug Delivery)

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Figure 1

Figure 1
Preparation of alginate capsules. (a) Alginate capsules were prepared by dropping 0.1, 0.25, 0.5, or 1% alginate solution (10 μL) into 1, 2.5, 5, 10, or 25% calcium chloride solution (2 mL). A 0.5% trypan blue solution was added to the sodium alginate solution at a ratio of 10%. (b) Bright-field and fluorescence images of an alginate capsule encapsulating 5 × 103 DiI-labeled C3H10T1/2 cells, prepared with 1% alginate solution and 10% calcium chloride solution. The scale bars indicate 500 μm. Full article ">Figure 2
Effect of the capsule size on the viability of encapsulated cells. Sodium alginate (10 mg) was dissolved in 1 mL phosphate-buffered saline (PBS) containing C3H10T1/2/Nluc cells at a density of 5 × 105 cells/mL. The alginate solution was collected using a micropipette, and 2.5, 5, 10, 25, or 50 μL of the collected solution was immersed in 10% calcium chloride solution for 10 s to prepare alginate capsules. (a) Typical image of capsules prepared using 2.5, 5, 10, 25, and 50 μL alginate solution (from left to right). (b) Relative light units in the culture supernatant of C3H10T1/2/Nluc cell-containing alginate capsules with different sizes. Results are expressed as the mean ± standard deviation (SD) (n = 3–4). Full article ">Figure 3
Effect of calcium chloride on the survival of encapsulated cells. Sodium alginate (10 mg) was dissolved in 1 mL phosphate-buffered saline (PBS) containing C3H10T1/2/Nluc cells at a density of 5 × 105 cells/mL. The alginate solution was immersed in 5 or 10% calcium chloride solution for 10 s, 30 s, 1 min, or 5 min to prepare the alginate capsules. The cell-encapsulated alginate capsules were cultured, and the relative light units in the culture supernatant was measured (a) every two days or (b) at 48 h. Results are expressed as the mean ± standard deviation (SD) (n = 4–6). The level of significance was measured using Student’s t-test (a) or ANOVA following Dunnett’s test compared to 10 s group (b) (ns: not significant, * p < 0.05). Full article ">Figure 4
Effect of the cell density on the survival of encapsulated cells. Sodium alginate (10 mg) was dissolved in 1 mL phosphate-buffered saline (PBS) containing C3H10T1/2/Nluc cells at a density of 1 × 104, 1 × 105, 5 × 105, 1 × 106, or 1 × 107 cells/mL. Each 10 μL alginate solution was immersed in 10% calcium chloride solution for 10 s to prepare alginate capsules. The cell-encapsulated alginate capsules were cultured, and the relative light units in the culture supernatant were measured every two days. Results are expressed as the mean ± standard deviation (SD) (n = 4). The level of significance was measured using ANOVA following Dunnett’s test compared to the 1 × 104 cells/mL group (* p < 0.05). Full article ">Figure 5
Survival and therapeutic effect of encapsulated cells after transplantation into mice. (a) Ten alginate capsules containing C3H10T1/2/Nluc cells at 5 × 103 cells/capsule were intraperitoneally transplanted in BALB/c-nu/nu mice. In addition, 5 × 104 suspended C3H10T1/2/Nluc cells were intraperitoneally transplanted. Relative light units in blood were measured. Results are expressed as the mean ± standard deviation (SD) (n = 4–6). The level of significance was measured using Student’s t-test compared to the suspended cell group (* p < 0.05). (b) Fifteen alginate capsules containing 5 × 104 MIN6 cells were intraperitoneally transplanted into C57BL/6 diabetic mice. Suspended MIN6 cells were intraperitoneally transplanted at a level of 7.5 × 105 cells. Blood glucose levels were measured. Results are expressed as the mean ± SD (n = 4–9). The level of significance was measured using ANOVA following Dunnett’s test compared to the sham-treated group (* p < 0.05). Full article ">

17 pages, 3102 KiB

Open AccessArticle

Intranasal Insulin Delivery: Microparticle Formulations Consisting of Aloe vera Polysaccharides for Advanced Delivery across Excised Olfactory and Respiratory Nasal Epithelial Tissues

by Cassandra Kirby-Smith, Jan Steenekamp, Dewald Steyn, Anja Haasbroek-Pheiffer, Hannlie Hamman and Josias Hamman

Appl. Sci. 2023, 13(8), 4822; https://doi.org/10.3390/app13084822 - 12 Apr 2023

Cited by 3 | Viewed by 2233

Abstract

Aloe vera gel and whole leaf materials, as well as polysaccharides, precipitated from the gel, have previously been shown to enhance macromolecular drug delivery across epithelial tissues. This study investigated the effectiveness of microparticle formulations prepared from A. vera polysaccharides for nasal delivery of insulin across excised sheep olfactory and respiratory nasal epithelial tissues. An emulsion-solvent evaporation technique was used to prepare two insulin microparticle formulations, namely one containing Eudragit^® L100 and A. vera polysaccharides and one containing A. vera polysaccharides only. In addition, an ionic gelation technique was used to prepare an insulin microparticle formulation with A. vera polysaccharides, where calcium chloride was used as a cross-linker. The microparticle formulations were evaluated in terms of drug content (assay), particle size, drug release (dissolution), ex vivo drug permeation, and histology. The microparticle formulations exhibited statistically significantly higher insulin delivery across excised sheep olfactory and respiratory nasal epithelial tissues compared to that of the control group (insulin alone). In conclusion, the use of A. vera polysaccharides in microparticle formulations significantly improved nasal insulin delivery. Therefore, A. vera polysaccharide containing microparticles showed high potential to enhance systemic bioavailability and delivery into the brain of macromolecular drugs such as insulin after intranasal administration. Full article

(This article belongs to the Special Issue Young Investigators in Advanced Drug Delivery)

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31 pages, 2144 KiB

Open AccessReview

A Well-Known Plant and New Therapeutic Strategies: Turmeric and Its Components in Oral Inflammatory Diseases Treatment

by Monika Wojtyłko, Paweł Kunstman, Hanna Bartylak, Łukasz Raszewski, Tomasz Osmałek and Anna Froelich

Appl. Sci. 2023, 13(13), 7809; https://doi.org/10.3390/app13137809 - 2 Jul 2023

Cited by 2 | Viewed by 3882

Abstract

Turmeric has been known for centuries as a spice and an important element of traditional medicine. Nowadays, plant-derived compounds are still an object of extensive scientific investigations aiming at the development of novel drugs and dosage forms. Turmeric and its most important component, curcumin, reveal numerous interesting biological properties, including antioxidant, anti-inflammatory and antimicrobial activity. Numerous scientific studies focusing on various aspects of the activity of turmeric-derived compounds show that curcuminoids display an enormous potential as active pharmaceutical ingredients useful in a wide spectrum of medical conditions. Oral diseases comprising both mild inflammations and severe life-threatening conditions are classified as the most common ones, affecting an enormous part of the global population. In this review, the current research regarding turmeric and its constituents in oral diseases is summarized and discussed, with special attention paid to novel findings and future directions regarding scientific exploration of curcuminoids. Full article

(This article belongs to the Special Issue Young Investigators in Advanced Drug Delivery)

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Figure 1
Structures of curcuminoids. Reproduced from [<a href="#B21-applsci-13-07809" class="html-bibr">21</a>] with permission. Full article ">Figure 2
Composition of turmeric rhizome [<a href="#B28-applsci-13-07809" class="html-bibr">28</a>]. Full article ">Figure 3
The most important mechanisms of antioxidant activities of curcumin; ROS—reactive oxygen species, RNS—reactive nitrogen species, SOD—superoxide dismutase, LOX—lipooxygenase, COX—cyclooxygenase, iNOS—inducible nitric oxide synthase, PG—prostaglandin, NO—nitric oxide. Full article ">Figure 4
Chemical structure of the common components of turmeric, other than curcumin. Reproduced from [<a href="#B78-applsci-13-07809" class="html-bibr">78</a>] with permission. Full article ">Figure 5
Antitumor effects of nanoparticles (PLGA NPs), free geftinib/curcumin combination (Free Gef/Cur) and coated nanoparticles (γ-PGA-Gef/Cur NPs) on SAS cell xenograft mice studies. Twenty male athymic BALB/c nu/nu mice were subcutaneously injected with SAS cells (1 × 107 cells/mouse) into one flank of each mouse. All animals were randomly divided into four groups (n = 5). Each animal was intraperitoneally injected with DMSO (control), PLGA NPs, free Cur/Gef or γ-PGA- Gef/Cur NPs every 2 days until the 22nd day. At the end of the experiment, all animals were anesthetized and sacrificed, and tumors were removed, photographed (A) and weighed (B). Data represent mean ± S.D.; p < 0.05 was a significant difference between drug/nanoparticle-treated and control groups. Reproduced from [<a href="#B156-applsci-13-07809" class="html-bibr">156</a>] with permission. Full article ">Figure 6
The tumor growth was inhibited with curcumin treatment in 4-nitroquinoline-oxide-induced mouse tongue carcinoma. (A) Scheme of treatment. Mice were given either 4NQO (50 μg/mL) or water in the drinking water for successive 16 weeks. Then, the mice were randomly divided into two groups and given curcumin or DMSO for 28 consecutive days. (B) The number of tumors per mouse in each group. The circles (Control) and triangles (Curcumin) were used to depict the number of animals with the particular number of tumors in each group. The data are represented as mean ± SEM, n = 8 (***, p < 0.001). (C) The volume of tumor per mouse in each group. The data are represented as mean ± SEM, n = 8 (***, p < 0.001). Reproduced from [<a href="#B183-applsci-13-07809" class="html-bibr">183</a>] with permission. Full article ">Figure 7
Effect of curcumin (CUR), 5-fluorouracil (5-FU) and doxorubicin (DOX) alone and in the combination treatments on NT8e cell survival by a colony-forming assay. After the treatment, the colonies were stained and photographed (A). The survival fraction NT8e cells after the respective treatments was represented (B); the values are presented as mean ± SD from three independent experiments (p < 0.05 statistically). a Control vs. CUR-FU and CUR-DOX, b 5-FU vs. CUR-5-FU and c DOX vs. CUR-DOX. Reproduced from [<a href="#B184-applsci-13-07809" class="html-bibr">184</a>] with permission. Copyright 2016 American Chemical Society. Full article ">

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