Transdermal delivery of amphotericin B using deep eutectic solvents for antifungal therapy

Abstract

Candida albicans is one of the most common pathogens causing invasive fungal infections, with a mortality rate of up to 20 %–50 %. Amphotericin B (AmB), a biopharmaceutics classification system (BCS) IV drug, significantly inhibits Candida albicans. AmB is primarily administered via oral and intravenous infusion, but severe infusion adverse effects, nephrotoxicity, and potential hepatotoxicity limit its clinical application. Deep eutectic solvents (DESs), with excellent solubilization ability and skin permeability, are attractive for transdermal delivery. Herein, we used DESs to deliver AmB for antifungal therapy transdermally. We first prepared and characterized DESs with different stoichiometric ratios of choline (Ch) and geranate (Ge). DESs increased the solubility of AmB by a thousand-fold. In vitro and in vivo, skin permeation studies indicated that DES_1:2 (Ch and Ge in 1:2 ratio) had the most outstanding penetration and delivered fluorescence dye to the dermis layer. Then, DES_1:2-AmB was prepared and in vitro antifungal tests demonstrated that DES_1:2-AmB had superior antifungal effects compared to AmB and DES_1:2. Furthermore, DES_1:2-AmB was skin-irritating and biocompatible. In conclusion, DES-AmB provides a new and effective therapeutic solution for fungal infections.