Calcofluor white-cholesteryl hydrogen succinate conjugate mediated liposomes for enhanced targeted delivery of voriconazole into Candida albicans

Abstract

Fungal infections gradually lead to a high mortality rate due to difficulties in diagnosis, the limited number of antifungal drugs available, and the appearance of resistant isolates. Here, we developed a calcofluor white-cholesteryl hydrogen succinate conjugate (CFW–CHSc) as a novel nanomaterial that specifically binds to chitin chains in the cell wall. We showed that fluorescent-dye loaded CFW–CHSc-liposomes entered the cytoplasm of Candida albicans cells with increased efficacy. Voriconazole-loaded CFW–CHSc-liposomes displayed an increased antifungal activity against C. albicans yeast cells in an in vitro assay. Animal infection models and animal imaging analysis showed that fluorescent-dye loaded CFW–CHSc-liposomes maintained prolonged residence in rodent tissues. In mouse liver and kidney tissue, voriconazole-loaded CFW–CHSc-liposomes showed significantly enhanced antifungal activity when administered intravenously. Taken together, our studies confirm that CFW–CHSc increases the drug delivery efficacy of nanoparticles in vitro by interacting with chitin chains in the C. albicans cell wall. The fungi-targeting nanoparticles improve the drug delivery efficacy in vivo by enriching the nanoparticles at the site of fungal infection via the blood circulation system. Fungi-targeting nanomaterials have a promising future in the treatment of nosomycosis.