Development of Ketoconazole-Loaded Transferosomal Hydrogel: Formulation Optimization and Evaluation for Enhanced Topical Antifungal Delivery

The present study focuses on the development and evaluation of a novel ketoconazole-loaded transferosomal hydrogel designed to enhance transdermal delivery for effective treatment of fungal infections. Transferosomes, flexible vesicular carriers composed of phospholipids and edge activators, were employed to improve drug encapsulation and skin penetration. A 3² full factorial design was used to optimize critical formulation parameters. The optimized vesicles were thoroughly characterized for particle size, zeta potential, entrapment efficiency, and other physicochemical properties. To enable topical application, the transferosomes were incorporated into a hydrogel matrix, which was subsequently for drug content estimation, viscosity, in vitro diffusion, and antifungal activity. Drug release followed the Higuchi model, characterized as a diffusion-controlled process where the drug moves from a polymeric matrix into the surrounding medium. An excellent match is indicated by the high R² value (R2 value of 0.9941), which confirms that Fickian diffusion through the hydrogel matrix. The results demonstrated that the transferosomal hydrogel exhibited zone of inhibition of 46mm and conventional formulation exhibited zone of inhibition of 30mm, transferosomal hydrogel exhibited superior antifungal efficacy against Candida albicans and significantly enhanced epidermal penetration and retention in contrast to traditional formulations. 85.86±5.68% of Transferosomal hydrogel drug was diffused through the goat skin while the marketed cream was only 45.78±2.56 diffused through the goat skin within 8 hours. These findings underscore the potential of this system as a promising and effective topical antifungal therapy.