Itraconazole lipid nanocapsules gel for dermatological applications: In vitro characteristics and treatment of induced cutaneous candidiasis

Abstract

There is a growing clinical demand for topical itraconazole (ITC) delivery systems because of the expanding potential of the drug for topical fungal and non-fungal applications. Lipid-based nanocarriers offer great promise in this respect. In the present study, a new topical ITC gel based on lipid nanocapsules (LNC) was developed. ITC-LNC were compared to ITC-loaded nanostructured lipid carriers (ITC-NLC) with more established benefits as topical vectors. Both nanocarriers showed high entrapment efficiency (EE > 98%). Compared to ITC-NLC, the ITC-LNC showed a significantly smaller particle size (∼50 vs 155 nm), narrower size distribution (0.09 vs 0.38), faster initial release rate under sink conditions and greater in vitro antifungal activity against Candida albicans (C. albicans) (inhibition zone 29.4 vs 26.4 mm). ITC-LNC and ITC-NLC-based gels significantly enhanced the dermal retention of ITC in excised human skin relative to a conventional ITC gel. Histopathological assessment of a 14-day treatment of induced cutaneous candidiasis in a rat model indicated efficacy of the gel preparations. Fungal elements developed in the superficial epidermal skin layer were cleared by the end of treatment. Equally important, no histopathological changes in the epidermal and dermal layers of rat skin were observed. Findings of this study verified efficacy of topical ITC in the treatment of superficial fungal infections as well as effectiveness of LNC as biomimetic nanocarrier for dermal drug delivery. Combining ITC and LNC would present a bioactive nanocarrier system with good potentials for fungal infections and other skin applications.