Preparation and evaluation of antifungal efficacy of griseofulvin loaded deformable membrane vesicles in optimized guinea pig model of Microsporum canis - Dermatophytosis

摘要

The present study is aimed at the encapsulation of griseofulvin in the deformable membrane vesicles (DMVs) for dermal delivery. Presently, griseofulvin is available only in conventional oral dosage forms that suffer from the issues of poor and highly variable bioavailability, numerous systemic side effects and long duration of treatment. Multi-lamellar drug-loaded DMVs of griseofulvin (Indian Patent Application 208/DEL/2009) were prepared by thin-film hydration method and were optimized for type and concentration of edge activator (EA). The optimized formulation was evaluated for vesicular shape, size, drug entrapment efficiency, drug content, pH, stability, spreadability, ex vivo skin permeation, dermatokinetics, skin sensitivity, in vitro antifungal assay and in vivo antifungal activity against Microsporum canis using guinea pig model for dermatophytosis. The optimized DMVs illustrated remarkably higher drug permeation and skin retention when compared with liposomes. A complete clinical and mycological cure was observed in animals treated with topical griseofulvin formulation in 10 days. The formulation was observed to be non-sensitizing, histopathologically safe, and stable at 5 ± 3 °C, 25 ± 2 °C and 40 ± 2 °C for a period of six months. The results indicated that the topical formulation of DMVs of griseofulvin could be utilized as an alternative to reduce the encumbrance of conventional oral formulations.