Formulation, Optimization, and Evaluation of Pegylated Bilosomes for the Topical Delivery of Luliconazole

Luliconazole is a promising candidate for the topical treatment of fungal infections. However, due to its poor skin permeability, effective management requires multiple administrations over a prolonged period. This study aimed to formulate, optimize, and evaluate luliconazole (LUL)-encapsulated pegylated bilosomes to enhance topical skin delivery. The formulation was developed and optimized using the thin-film hydration technique, employing a Box-Behnken Design (BBD). The optimized LUL-loaded pegylated bilosomes were spherical with a particle size of 270 ± 4 nm, a polydispersity index (PDI) of 0.4 ± 0.025, a zeta potential (ZP) of − 48.7 ± 1.99 mV, and an entrapment efficiency (EE%) of 94.0 ± 1.95%. Spectral analysis and thermogram studies confirmed effective encapsulation of the drug within the vesicular carrier and indicated a high deformability index. The in vitro antifungal activity of optimized formulation (***p < 0.001) demonstrated significant inhibition of Candida albicans. Ex vivo skin permeation and confocal laser scanning microscopy studies demonstrated enhanced penetration of the drug into deeper epidermal layers compared to conventional niosomes. In vivo pharmacodynamic studies in Wistar albino rats revealed a greater reduction in signs and symptoms of infection with the optimized formulation than with other formulations. These findings suggest that pegylated bilosomes may serve as a promising vesicular carrier for LUL and potentially other antifungal agents for targeted skin delivery, offering improved therapeutic outcomes in topical treatment.