TL;DR
The developed thermosensitive in-situ nanoemulsion gel can be a candidate for presenting an innovative and effective platform for the prolonged topical delivery of lidocaine and prilocaine with favorable physicochemical and stability properties.
Introduction The present study aimed to develop and evaluate a thermoresponsive in situ gel incorporating Exemestane-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles for sustained drug delivery. Methods Exemestane-loaded PLGA nanoparticles were prepared by nanoprecipitation and characterised for particle size, zeta potential, morphology, entrapment efficiency, and drug release behaviour. Results The nanoparticle exhibited a mean particle size of 257.6 nm, moderate stability with a zeta potential of–15.3mV, high encapsulation efficiency (93.46± 2.46%) and drug loading 27.8±1.2% (0.278±0.012mg Exemestane /mg nanoparticles), indicating successful formulation. The optimised nanoparticles were incorporated into a poloxamer-based thermoresponsive in situ gel system modified with chitosan to enhance gel strength and bioadhesion. The formulation was optimised using a Box–Behnken design, achieving a gelation temperature of 38.3±0.5 °C and gelation time of 0.75±0.5 min, suitable for physiological conditions. In vitro drug release studies demonstrated a sustained release profile with minimal burst effect, achieving approximately 80% drug release over 24 hours. Release kinetics followed the Korsmeyer–Peppas model, indicating an Fickian and diffusion mechanism governed by both diffusion and polymer erosion.The formulation exhibited desirable physicochemical properties, appropriate rheological behaviour, controlled gel erosion, and stability over three months.Ex vivo and HET-CAM studies indicated reduced angiogenesis, suggesting potential therapeutic efficacy in breast cancer treatment. Discussion Overall, the developed nanoparticle-loaded thermoresponsive in situ gel represents a promising localised sustained drug delivery platform for Exemestane and warrants further evaluation in appropriate cellular and in vivo breast cancer models.
The therapeutic efficiency of topical antifungal drops is limited due to rapid precorneal clearance and short residence time, which reduce drug bioavailability at the site of infection so this study aimed to develop and evaluate a thermosensitive in situ gelling nanoemulsion of fluconazole for enhanced ophthalmic delivery and prolonged ocular retention. Pseudo-ternary phase diagrams were constructed by using Triacetin as the oil, Propylene glycol as the co-surfactant, Cremophor ® RH 40 as the surfactant and water to determination of the O/W nanoemulsion region and optimize formulation composition. Six prepared fluconazole-loaded nanoemulsions were characterized by droplet size, poly disperse index (PDI), refractive index (RI), pH and viscosity. The selected formulation was developed for thermosensitive nanoemulsion by using Poloxamer 188 & 407. Optimized sample was evaluated for release, stability and antifungal activity. The optimized nanoemulsion with 5% of Triacetin, 5% Cremophor ® RH 40 and 5% Propylene glycol and 0.3% fluconazole exhibited a mean droplet size of approximately 15 nm with a PDI of 0.270, indicating a homogeneous nanosystem with a narrow size distribution. The formulation demonstrated viscosity around 3 cp and underwent a rapid sol-to-gel transition at 33.6°C, closely matching the physiological temperature of the ocular surface. In vitro release studies revealed a sustained release profile, with 59.71% of fluconazole released over 8 h. Furthermore, the formulation exhibited notable antifungal activity, producing an inhibition zone of 33 mm against the tested fungal strain. In conclusion, the optimized thermo-sensitive in situ gelling nanoemulsion demonstrated favorable physicochemical characteristics, sustained drug release, satisfactory stability, and effective antifungal activity. These findings suggest that the proposed delivery system represents a promising strategy for improving the ocular bioavailability and therapeutic efficacy of fluconazole in the treatment of fungal eye infections.
A series of semaglutide-loaded sustained-release formulations is developed using thermosensitive hydrogel as the release system. Micro-needle jet injection (MNJI) devices are used to deliver the highly viscous material and achieve a desired dispersion at delivery. Physicochemical properties, in vitro drug release behavior, and biocompatibility are systematically characterized. Therapeutic efficacy is evaluated in DIO rats, with non-sustained formulation as control to assess efficacy and sustainability.P407-based hydrogel has temperature-dependent sol-gel transition: at low temperature it is injectable, while at body temperature it becomes a solid gel to restrict semaglutide release. Drug incorporation did not interfere with this property. MNJI devices effectively delivered the formulation with consistency and showed favorable safety without severe inflammation. The system prolonged half-life to 15 h, extended Tmax from 8 to 24 h, and maintained effective levels to day 6. In DIO rats, GT10 50 achieved continuous weight loss over 20 days, overcoming the plateau of non-sustained formulations. Serum assays revealed significant reductions in TC (P < 0.01), ALT (P < 0.05), and AST (P < 0.01), indicating improved dyslipidemia and liver injury. Glucose tolerance tests confirmed alleviation of hyperglycemia without hypoglycemia. This study provides a strategy for obesity management with good efficacy and improved compliance via reduced dosing.
The present study aimed to develop and evaluate sustained -release matrix tablets of Trazodone Hydrochloride using a hydrophilic matrix system to achieve prolonged drug release and improve patient compliance. Preformulation studies were carried out to characterize the drug, including particle size analysis, melting point determination, UV spectroscopy, FTIR spectroscopy, and differential scanning calorimetry (DSC). Drug – excipient compatibility studies confirmed the absence o f significant interactions between Trazodone Hydrochloride and the selected excipients. Seven formulations (F1 – F7) were prepared by direct compression using varying concentrations of release - retarding polymers. The powder blends were evaluated for micromer itic properties, showing good flowability and compressibility with Carr’s index below 15%, Hausner’s ratio below 1.20, and angle of repose below 30°. The compressed tablets were assessed for weight variation, hardness, thickness, friability, drug content, and in vitro dissolution performance. All formulations complied with pharmacopoeial requirements.Among the developed formulations, F5 demonstrated the most desirable sustained -release characteristics, exhibiting 38.4% drug release at 4 h, 63.4% at 8 h, 80.5% at 12 h, and 98.8% at 24 h. The formulation also showed excellent tablet properties, including opti mum hardness (5.8 kg/cm²), low friability (0.42%), and high drug content (99.82%). Drug release kinetic modelling revealed that the optimized formulation followed the Higuchi model (R² = 0.996), indicating diffusion - controlled drug release. The Korsmeyer – P eppas release exponent (n = 0.63) suggested a non - Fickian diffusion mechanism involving both diffusion and polymer relaxation.Accelerated stability studies conducted at 40 ± 2°C/75 ± 5% RH for three months demonstrated that the optimized formulation remained physically and chemically stable, with negligible changes in drug content and dissolution profile. The study concludes that sustained -release matrix tablets of Trazodone Hydrochloride can be successfully formulated using an appropriate polymer matrix system to provide controlled drug release over 24 hours.
Background: Topical drug delivery systems provide site-specific therapy with reduced systemic exposure. Nanosponges have emerged as promising carriers owing to their porous structure, enabling improved drug stability, bioavailability, and sustained release. Apremilast, a phosphodiesterase-4 (PDE4) inhibitor with anti-inflammatory activity, has potential for topical wound management when formulated as a controlled-release delivery system. Methods: Apremilast-loaded nanosponges were prepared by the emulsion solvent diffusion method using Ethyl Cellulose (EC) and Polyvinyl Alcohol (PVA). A 3² factorial design was used to optimize the EC: PVA ratio and sonication time. Formulations were evaluated for particle size, entrapment efficiency, zeta potential, in vitro drug release, and surface morphology. Characterization included UV spectroscopy, FTIR, XRD, DSC, and SEM. Drug release kinetics were analyzed using mathematical models. Results: Preformulation studies confirmed drug purity and compatibility with excipients. The optimized formulation (NS8) exhibited a particle size of 213.85 nm, an entrapment efficiency of 82.75%, a zeta potential of −33.3 mV, and a sustained drug release of 95.85% over 24 h. SEM revealed spherical porous nanosponges, while FTIR, XRD, and DSC confirmed drug integrity and formulation stability. Response surface analysis demonstrated significant effects of formulation variables on performance. Drug release followed the Higuchi model (R² = 0.987), and the Korsmeyer–Peppas exponent (n = 0.58) indicated anomalous non-Fickian diffusion. Conclusion: Apremilast-loaded nanosponges demonstrated sustained drug release, excellent stability, and favorable physicochemical characteristics, indicating their potential as an effective topical delivery system for wound management. Further ex vivo, in vivo, and clinical studies are required to confirm therapeutic efficacy and safety.
