ABSTRACT
Objectives: Rutin has been broadly applied for treating several diseases due to its pharmacological activities. However, its low aqueous solubility limits its absorption and bioavailability. This research aims to increase the solubility of rutin using cyclodextrin and to develop a temperature-triggered in situ gelling system for dermal application. Materials and Methods: The solubility of rutin was increased with sulfobutyl ether-ß-cyclodextrin (SBE-ß-CD). Rutin- SBE-ß-CD inclusion complex was prepared by kneading and freeze dying method. Structural characterization was carried out using differential scanning calorimetry and fourier transform infrared spectroscopy. In situ gel formulations were prepared with pluronic F127 (PF127), a thermosensitive polymer, and chitosan (CH), a natural, biodegradable, and mucoadhesive hydrophilic polymer. In situ gel characteristics such as pH, clarity, gelation temperature, and viscosity were determined. Results: When the solubility diagrams were examined, it was concluded that SBE-ß-CD showed a linear increase, therefore, AL-type diagram was selected. The formulations were produced using different amounts of PF127 and a fixed ratio of CH. Three in situ gels were evaluated for their pH, gelling temperature, and the rheological behaviors, and one formulation was selected. It was observed that the formulations had a pH between 6-6.1, and their gelation temperature decreased with increasing PF127 that was between 20°C to 34°C. For the selected formulation (formulation E3), 0.5% rutin and rutin/SBE-ß-CD were transferred to the in situ gelling system. Because of in vitro release studies, it was observed that the release of the rutin/SBE-ß-CD inclusion complex containing NZ formulation showed a higher burst effect than the others and the release continued for 6 hours. Conclusion: The results indicated that the combination of PF127 and CH can be a hopeful in situ gelling vehicle for dermal delivery of rutin and rutin/SBE-ß-CD.
ABSTRACT
Infection with the human immunodeficiency virus (HIV) is affecting women disproportionally with increasing incidence rates over the last decades. Tenofovir is one of the most commonly used antiretroviral agents, which belongs to the nucleoside/nucleotide reverse transcriptase inhibitor family, for the prevention of HIV acquisition. In scope of this study, a thermogelling system containing tenofovir-loaded chitosan nanoparticles for the controlled release of tenofovir was developed and characterized. The in vitro release studies have shown that the burst release effect was decreased to 27% with f-TFV CS NPs-Gel. Gelation temperature of developed formulation was found as 26.6 ± 0.2 °C, which provides ease of administration while gelation occurs after the administration to the vagina. The work of adhesion values was used as parameters for comparison of mucoadhesive performance and the mucoadhesion of f-TFV CS NPs-Gel was found as 0.516 ± 0.136 N.s at 37 °C. The biocompatibility of blank formulations was evaluated by cell viability studies using L929 cells, in which Gel + CS NPs formulation was found to be safe with 82.4% and 90.2% cell viability for 1:16 and 1:32 dilutions, respectively. In conclusion, an improved tenofovir containing vaginal gel formulation was successfully developed and evaluated for preventing HIV transmission.
