Search Results (77)

Pyrimidine derivatives exhibit a wide range of biological activities, including anti-inflammatory properties. The aim of this study was to investigate the effects of tested pyrimidine derivatives on the activity of cyclooxygenase isoenzymes (COX-1 and COX-2), antioxidant properties, and their ability to inhibit the growth of inflammatory cells. In vitro tests were conducted to assess the ability of pyrimidine derivatives L1–L4 to inhibit COX-1 and COX-2 activity using the TMPD oxidation assay (N,N,N',N'-tetramethyl-p-phenylenediamine). The compounds’ ability to inhibit the growth of lipopolysaccharide (LPS)-stimulated THP-1 (human leukemia monocytic) monocyte cells and their impact on reactive oxygen species (ROS) levels in an inflammatory model were also evaluated. The binding properties of human serum albumin (HSA) were assessed using UV–Vis spectroscopy, circular dichroism (CD), and isothermal titration calorimetry (ITC). Among the tested pyrimidine derivatives, L1 and L2 showed high selectivity towards COX-2, outperforming piroxicam and achieving results comparable to meloxicam. In the sulforhodamine B (SRB) assay, L1 and L2 demonstrated dose-dependent inhibition of LPS-stimulated THP-1 cell growth. Additionally, ROS assays indicated that these compounds reduced free radical levels, confirming their antioxidant properties. Binding studies with albumin revealed that L1 and L2 formed stable complexes with HSA. These results suggest that these compounds could serve as a basis for further research into anti-inflammatory and anticancer drugs with reduced toxicity. Full article

Objectives: This systematic review was designed to summarize randomized controlled trials of intra-articular administration of non-steroidal anti-inflammatory drugs (NSAIDs) for temporomandibular disorders. Methods: Randomized controlled trials regarding intra-articular injections of non-steroidal anti-inflammatory drugs for temporomandibular disorders were included in the review. The final search was conducted on 16 June 2024 in the Bielefeld Academic Search Engine, PubMed, and Scopus databases. Results: Of the 173 identified studies, 6 were eligible for review. In trials comparing arthrocentesis alone to arthrocentesis with NSAIDs, slight differences in joint pain were noted. For tenoxicam, differences were under 1 point on a 0–10 scale after 4 weeks, with inconsistent results. Piroxicam showed no significant difference, and pain levels were minimal in both groups. For maximum mouth opening (MMO), tenoxicam showed no significant difference. Piroxicam increased MMO by nearly 5 mm, based on one small trial with bias concerns. Conclusions: Currently, there is no strong scientific evidence supporting the injection of NSAIDs into the temporomandibular joint to relieve pain or increase jaw movement. Preliminary reports on piroxicam with arthrocentesis and tenoxicam or diclofenac without rinsing justify further research. Full article

This rapid review summarizes the latest primary research in temporomandibular joint (TMJ) injection treatment. The final literature searches were conducted on 4 January 2024. Selection was performed systematically following predefined eligibility criteria. Randomized control trials concerning the treatment of TMJ disorders with intra-articular injections were included. Studies on more invasive interventions were excluded. Quality of life, joint pain and range of mandibular mobility were assessed. Ultimately, 12 studies covering a total of 603 patients qualified. They concerned: (1) arthrocentesis (AC) and the administration of, (2) injectable platelet-rich fibrin (I-PRF), (3) platelet-rich plasma (PRP), (4) hyaluronic acid (HA), (5) non-steroidal anti-inflammatory drugs (NSAIDs), and (6) hypertonic dextrose (HD) with a local anesthetic. The dominant approach was to perform arthrocentesis before administering the appropriate injection substance (I-PRF, PRP, HA, or NSAID). Two current studies on the intra-articular administration of NSAIDs, specifically tenoxicam and piroxicam, are noteworthy. A mixture of PRP and HA was injected in another two trials. These two innovative approaches may prove to be significant directions for further research on injection treatment of TMJs. Full article

The antifungal agent, ketoconazole, and the anti-inflammatory drug, piroxicam, were incorporated into matrices of xanthan or oleic acid-esterified xanthan (Xn) and polyurethane (PU), to develop topical drug delivery systems. Compared to matrices without bioactive compounds, which only showed a nominal compressive stress of 32.18 kPa (sample xanthan–polyurethane) at a strain of 71.26%, the compressive resilience of the biomaterials increased to nearly 50.04 kPa (sample xanthan–polyurethane–ketoconazole) at a strain of 71.34%. The compressive strength decreased to around 30.67 kPa upon encapsulating a second drug within the xanthan–polyurethane framework (sample xanthan–polyurethane–piroxicam/ketoconazole), while the peak sustainable strain increased to 87.21%. The Weibull model provided the most suitable fit for the drug release kinetics. Unlike the materials based on xanthan–polyurethane, those made with oleic acid-esterified xanthan–polyurethane released the active ingredients more slowly (the release rate constant showed lower values). All the materials demonstrated antimicrobial effectiveness. Furthermore, a higher volume of piroxicam was released from oleic acid-esterified xanthan–polyurethane–piroxicam (64%) as compared to xanthan–polyurethane–piroxicam (44%). Considering these results, materials that include polyurethane and either modified or unmodified xanthan showed promise as topical drug delivery systems for releasing piroxicam and ketoconazole. Full article

In this paper, a self-assembly method was used to prepare gold nanorod composites, and a seed-growth method was used to adjust the amount of AgNO₃ solution, enabling the preparation of gold nanorods with different aspect ratios. AuNRs@SiO₂ nanocomposite particles were then prepared by using the Stöber method to coat the gold nanorod surface with silica. Transmission electron microscopy showed that the maximum aspect ratio of the gold nanorods was 4.53, which was achieved using 2 mL of 10 mM AgNO₃ solution. The Raman-scattering intensity of the gold nanorods was studied using rhodamine 6G, thiram, melamine, and piroxicam, and detection limits of 10⁻⁸ M, 10⁻⁵ M, and 10⁻³ M were, respectively, achieved. As a substrate, these gold nanorods showed good repeatability and reproducibility, and trace detection was successfully achieved. A transmission electron microscopy analysis shows that the SiO₂ shell became thicker with increasing tetraethyl orthosilicate addition. Using AuNRs@SiO₂ as the base and R6G, thiram, and piroxicam as the probes, measurable detection limits of 10⁻⁹ M, 10⁻⁶ M, and 10⁻⁵ M were achieved, and this composite also showed excellent repeatability and reproducibility. Full article

Non-steroidal anti-inflammatory piroxicam (PRX) is a poorly water-soluble drug that provides relief in different arthritides. Reducing the particle size of PRX increases its bioavailability. For pediatric, geriatric, and dysphagic patients, oral dispersible systems ease administration. Moreover, fast disintegration followed by drug release and absorption through the oral mucosa can induce rapid systemic effects. We aimed to produce an orodispersible lyophilizate (OL) consisting of nanosized PRX. PRX was solved in ethyl acetate and then sonicated into a poloxamer-188 solution to perform spray-ultrasound-assisted solvent diffusion-based nanoprecipitation. The solid form was formulated via freeze drying in blister sockets. Mannitol and sodium alginate were applied as excipients. Dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) were used to determine the particle size. The morphology was characterized by scanning electron microscopy (SEM). To establish the crystallinity, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used. A disintegration and in vitro dissolution test were performed. DLS and NTA presented a nanosized PRX diameter. The SEM pictures showed a porous structure. PRX became amorphous according to the XRPD and DSC curves. The disintegration time was less than 1 min and the dissolution profile improved. The final product was an innovative anti-inflammatory drug delivery system. Full article

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most prescribed drugs to treat pain or fever. However, oral administration of NSAIDs is frequently associated with adverse effects due to their inhibitory effect on the constitutively expressed cyclooxygenase enzyme 1 (COX-1) in, for instance, the gastrointestinal tract. A systemic delivery, such as a buccal delivery, of NSAIDs would be beneficial and additionally has the advantage of a non-invasive administration route, especially favourable for children or the elderly. To investigate the transport of NSAIDs across the buccal mucosa and determine their potential for buccal therapeutic usage, celecoxib, diclofenac, ibuprofen and piroxicam were tested using an established oral mucosa Transwell^® model based on human cell line TR146. Carboxyfluorescein and diazepam were applied as internal paracellular and transcellular marker molecule, respectively. Calculated permeability coefficients revealed a transport ranking of ibuprofen > piroxicam > diclofenac > celecoxib. Transporter protein inhibitor verapamil increased the permeability for ibuprofen, piroxicam and celecoxib, whereas probenecid increased the permeability for all tested NSAIDs. Furthermore, influence of local inflammation of the buccal mucosa on the transport of NSAIDs was mimicked by treating cells with a cytokine mixture of TNF-α, IL-1ß and IFN-γ followed by transport studies with ibuprofen (+ probenecid). Cellular response to pro-inflammatory stimuli was confirmed by upregulation of cytokine targets at the mRNA level, increased secreted cytokine levels and a significant decrease in the paracellular barrier. Permeability of ibuprofen was increased across cell layers treated with cytokines, while addition of probenecid increased permeability of ibuprofen in controls, but not across cell layers treated with cytokines. In summary, the suitability of the in vitro oral mucosa model to measure NSAID transport rankings was demonstrated, and the involvement of transporter proteins was confirmed; an inflammation model was established, and increased NSAID transport upon inflammation was measured. Full article

Hot melt extrusion (HME) offers a high-throughput process to manufacture amorphous solid dispersions. A variety of experimental and model-based approaches exist to predict API solubility in polymer melts, but these methods are typically aimed at determining the thermodynamic solubility and do not take into account kinetics of dissolution or the associated degradation of the API during thermal processing, both of which are critical considerations in generating a successful amorphous solid dispersion by HME. This work aims to develop a material-sparing approach for screening manufacturability of a given pharmaceutical API by HME using physically relevant time, temperature, and shear. Piroxicam, ritonavir, and phenytoin were used as model APIs with PVP VA64 as the dispersion polymer. We present a screening flowchart, aided by a simple custom device, that allows rapid formulation screening to predict both achievable API loadings and expected degradation from an HME process. This method has good correlation to processing with a micro compounder, a common HME screening industry standard, but only requires 200 mg of API or less. Full article

Lipid and/or polymer-based drug conjugates can potentially minimize side effects by increasing drug accumulation at target sites and thus augment patient compliance. Formulation factors can present a potent influence on the characteristics of the obtained systems. The selection of an appropriate solvent with satisfactory rheological properties, miscibility, and biocompatibility is essential to optimize drug release. This work presents a computational study of the effect of the basic formulation factors on the characteristics of the obtained in situ-forming particulates (IFPs) encapsulating a model drug using a 2¹.3¹ full factorial experimental design. The emulsion method was employed for the preparation of lipid and/or polymer-based IFPs. The IFP release profiles and parameters were computed. Additionally, a desirability study was carried out to choose the optimum formulation for further morphological examination, rheological study, and PBPK physiological modeling. Results revealed that the type of particulate forming agent (lipid/polymer) and the incorporation of structure additives like Brij 52 and Eudragit RL can effectively augment the release profile as well as the burst of the drug. The optimized formulation exhibited a pseudoplastic rheological behavior and yielded uniformly spherical-shaped dense particulates with a PS of 573.92 ± 23.5 nm upon injection. Physiological modeling simulation revealed the pioneer pharmacokinetic properties of the optimized formulation compared to the observed data. These results assure the importance of controlling the formulation factors during drug development, the potentiality of the optimized IFPs for the intramuscular delivery of piroxicam, and the reliability of PBPK physiological modeling in predicting the biological performance of new formulations with effective cost management. Full article

It was recently shown that targeting extracellular vimentin (eVim) is safe and effective in preclinical models. Here, we report the safety and efficacy in client-owned dogs with spontaneous bladder cancer of CVx1, an iBoost technology-based vaccine targeting eVim in combination with COX-2 inhibition. This was a single-arm prospective phase 1/2 study with CVx1 in 20 client-owned dogs with spontaneous UC which involved four subcutaneous vaccinations with CVx1 at 2-week intervals for induction of antibody titers, followed by maintenance vaccinations at 2-month intervals. Additionally, daily cyclooxygenase (COX)-2 inhibition with meloxicam was given. The response was assessed by antibody titers, physical condition, abdominal ultrasound and thorax X-ray. The primary endpoints were the development of antibody titers, as well as overall survival compared to a historical control group receiving carboplatin and COX-2 inhibition with piroxicam. Kaplan–Meier survival analysis was performed. All dogs developed antibodies against eVim. Titers were adequately maintained for the duration of this study. A median overall survival of 374 days was observed, which was 196 days for the historical control group (p < 0.01). Short-term grade 1–2 toxicity at the injection site and some related systemic symptoms peri-vaccination were observed. No toxicity was observed related to the induced antibody response. A limitation of this study is the single-arm prospective setting. CVx1 plus meloxicam consistently induced efficient antibody titers, was well tolerated and showed prolonged survival. The results obtained merit further development for human clinical care. Full article

Oral surgery, such as tooth extractions and dental implantations, can cause inflammation in the surrounding tissue, especially in bones. Anti-inflammatory drugs are crucial for pain relief and wound healing. Nonsteroidal anti-inflammatory drugs (NSAIDs) and light-emitting diode irradiation (LEDI) at 625 nm have been used as therapies to reduce inflammation, which ultimately promotes wound healing. The mechanism of these two methods, however, is different, which possibly makes the combined use of the two approaches effective. Therefore, the efficacy of 625 nm LEDI, NSAIDs, or a combination of both on anti-inflammatory and wound healing effects were analyzed in MC3T3-E1. In this study, piroxicam, ibuprofen, indomethacin, and celecoxib were selected as the NSAIDs. The effect of LEDI at 625 nm was investigated by cell viability, prostaglandin E₂ (PGE₂) release, and the expression of inflammation-related proteins and cell migration-related proteins were evaluated. Additionally, alkaline phosphatase staining with activity, cell migration assay and BrdU cell proliferation assays were performed. Both LEDI and NSAIDs reduced cyclooxygenase-2 (COX-2) and PGE₂. Additionally, LEDI promoted cell migration, proliferation, and bone formation as well, but not by NSAIDs. Thus, a combination of LEDI and NSAIDs can benefits the cells in inflammation, which provides upturn strategies for bone healing after tooth extraction. Full article

Chrysin (5,7-dihydroxyflavone) has many pharmacological properties including anti-inflammatory actions. The objective of this study was to evaluate the anti-arthritic activity of chrysin and to compare its effect with the non-steroidal anti-inflammatory agent, piroxicam, against complete Freund’s adjuvant (CFA)-induced arthritis in a pre-clinical model in rats. Rheumatoid arthritis was induced by injecting CFA intra-dermally in the sub-plantar region of the left hind paw of rats. Chrysin (50 and 100 mg/kg) and piroxicam (10 mg/kg) were given to rats with established arthritis. The model of arthritis was characterized using an index of arthritis, with hematological, biological, molecular, and histopathological parameters. Treatment with chrysin significantly reduced the arthritis score, inflammatory cells, erythrocyte sedimentation rate, and rheumatoid factor. Chrysin also reduced the mRNA levels of tumor necrosis factor, nuclear factor kappa-B, and toll-like recepter-2 and increased anti-inflammatory cytokines interleukin-4 and -10, as well as the hemoglobin levels. Using histopathology and microscopy, chrysin reduced the severity of arthritis in joints, infiltration of inflammatory cells, subcutaneous inflammation, cartilage erosion, bone erosion, and pannus formation. Chrysin showed comparable effects to piroxicam, which is used for the treatment of rheumatoid arthritis. The results showed that chrysin possesses anti-inflammatory and immunomodulatory effects that make it a potential drug for the treatment of arthritis. Full article

Piroxicam is a Biopharmaceutical Classification System (BCS) Class II drug having poor aqueous solubility and a short half-life. The rationale behind the present research was to develop a Piroxicam nanosuspension to enhance the solubility and thereby the in vitro bioavailability of the drug. Piroxicam nanosuspension (PRX NS) was prepared by an anti-solvent precipitation technique and optimized using a full-factorial design. Herein, the nanosuspension was prepared using polymer polyvinylpyrrolidone (PVP) K30^® and Poloxamer 188^® as a stabilizer to improve the solubility and in vitro bioavailability of the drug. Nine formulations were prepared based on 3² full-factorial experimental designs to study the effect of the formulation variables such as concentration of poloxamer 188 (%) (X₁) and stirring speed (rpm) (X₂) as a process variable on the response of particle size (nm) and solubility (µg/mL). The prepared NS was characterized by phase solubility, Fourier-transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), transmission electron microscopy (TEM), particle size, zeta potential, entrapment efficiency, and percent drug release. DSC and XRPD analysis of freeze-dried NS formulation showed conversion of PRX into a less crystalline form. NS formulations showed a reduction in the size from 443 nm to 228 nm with −22.5 to −30.5 mV zeta potential and % drug entrapment of 89.76 ± 0.76. TEM analysis confirmed the size reduction at the nano level. The solubility was increased from 44 μg/mL to 87 μg/mL by altering the independent variables. The solubility of PRX NS in water was augmented by 14- to 15-fold (87.28 μg/mL) than pure PRX (6.6 μg/mL). The optimized formulation (NS9) at drug-to-stabilizer concentration exhibited a greater drug release of approximately 96.07% after 120 min as compared to the other NS formulations and pure PRX (36.78%). Thus, all these results revealed that the prepared NS formulations have improved the solubility and in vitro dissolution compared to the pure drug. Furthermore, an increase in the drug release was observed from the NS than that of the pure PRX. All these outcomes signified that the prepared PRX NS showed an increase in solubility and in vitro dissolution behavior; which subsequently would aid in attainment of enhanced bioavailability. Full article

The objectives of this study are the synthesis of thermosensitive poly(N-isopropylacrylamide-co-2-hydroxypropyl methacrylate), p(NiPAm-HPMet), hydrogels and the analysis of a drug-delivery system based on piroxicam, as a model drug, and synthesized hydrogels. A high pressure liquid chromatography method has been used in order to determine both qualitative and quantitative amounts of unreacted monomers and crosslinkers from polymerized hydrogels. Swelling kinetics and the order of a swelling process of the hydrogels have been analyzed at 10 and 40 °C. The copolymers’ thermal properties have been monitored by the differential scanning calorimetry (DSC) method. DSC termograms have shown that melting occurs in two temperature intervals (142.36–150.72 °C and 153.14–156.49 °C). A matrix system with incorporated piroxicam has been analyzed by using FTIR and SEM methods. Structural analysis has demonstrated that intermolecular non-covalent interactions have been built between side-groups of copolymer and loaded piroxicam. Morphology of p(NiPAm-HPMet) after drug incorporation indicates the piroxicam presence into the copolymer pores. Kinetic parameters of the piroxicam release from hydrogels at 37 °C and pH 7.4 indicate that the fluid transport mechanism corresponds to Fickian diffusion. As a result, formulation of thermosensitive p(NiPAm-HPMet) hydrogels with incorporated piroxicam could be of interest for further testing as a drug carrier for modulated and prolonged release, especially for topical administration. Full article

Knee osteoarthritis (OA) is the most common joint disease. The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) by phonophoresis is a therapeutic alternative to relieve pain in inflammatory pathologies. The main aim was to analyze the efficacy of the application of NSAIDs by phonophoresis in knee OA. A systematic review and meta-analysis of controlled clinical trials were performed between January and March 2021 in the following databases: Web of Science, Scopus, PubMed, Cinahl, SciELO, and PEDro. The PEDro scale was used to evaluate the level of evidence of the selected studies. The RevMan 5.4 statistical software was used to obtain the meta-analysis. Eight studies were included, of which five were included in the meta-analysis, involving 195 participants. The NSAIDs used through phonophoresis were ibuprofen, piroxicam, diclofenac sodium, diclofenac diethylammonium, ketoprofen, and methyl salicylate. The overall result for pain showed not-conclusive results, but a trend toward significance was found in favor of the phonophoresis group compared to the control group (standardized mean difference (SMD) = −0.92; 95% confidence interval: −1.87–0.02). Favorable results were obtained for physical function (SMD = −1.34; 95% CI: −2.00–0.68). Based on the selected studies, the application of NSAIDs by phonophoresis is effective in relieving the symptoms of knee OA. Future long-term studies are recommended. Full article