Development, characterization and preclinical evaluation of nanosized liposomes of itraconazole for topical application: 32 full factorial design to estimate the relationship between formulation components

The objective of the study was to statistically develop a novel formulation of itraconazole (ITZ) loaded nanosized liposomes (NLPs) for effective topical delivery against superficial fungal infections. Target formulation was prepared by thin-film hydration, and was optimized by employing a two-step design of experiments (DoE) approach, which comprised a fractional factorial design for screening of 'vital few' factors, and response surface mapping optimized using a fractional factorial and 3(2) full factorial design of experiments. Overlay of response maps for percent drug entrapment (PDE), vesicle size, ITZ skin retention and permeation performed to obtain the optimized ITZ loaded NLPs (OPT-NLPs) suspension. The liposome suspension was gelled to improve topical applicability. OPT-NLPs formulation was able to show high PDE (78.69 +/- 3.17%), and average vesicle size of 358.2 +/- 9.45 nm and mean zeta potential of 20.66 +/- 0.74 mV were observed. Additionally, noticeably higher ITZ skin retention (44.39 +/- 1.32 mu g/cm(2)) and cumulative 6-h drug permeation (14.81 +/- 0.48 mu g/cm(2)) were observed in excised rat skin in comparison to conventional cream and oily solution of ITZ. Also, standardized Tinea pedis animal model was used to evaluate in vivo antifungal efficacy observed in terms of physical manifestations, fungal-burden score and histopathological profiles. Rapid alleviation of infection in animals treated with optimized hydrogel was observed in comparison to those treated with commercial topical and oral antifungal therapies. Our study suggests that the developed formulation may be a promising and rapid alternative to conventional antifungal therapies against dermatophytosis.

Automated summary

The study developed an optimized formulation of itraconazole loaded nanosized liposomes for effective treatment against superficial fungal infections. In vitro and in vivo experiments demonstrated high drug entrapment, micrometer-sized vesicles, high skin retention and drug permeation qualities of the formulation. The optimized hydrogel showed rapid alleviation of infection in animal models compared to commercial antifungal therapies.