Nanoscale fluconazole-constructed metal-organic frameworks with smart drug release for eradication of Candida biofilms in vulvovaginitis infection

Abstract

Fungal infections associated with oral, gynecological, and skin ailments pose significant clinical challenges. The presence of biofilms often hampers the efficacy of conventional antifungal drugs owing to the complex microenvironment they create. In this study, the widely used antifungal medication fluconazole is utilized as a foundational component to be incorporated into zinc 2-methylimidazolate frameworks, resulting in the synthesis of nanoscale fluconazole-constructed metal-organic frameworks (F-ZIF). The F-ZIF is constructed through coordination interactions between zinc and fluconazole, retaining the structure and pH-responsiveness of the zinc 2-methylimidazolate framework. The pH-responsiveness F-ZIF makes sure the fluconazole can be released in acidic biofilm, which prevents the undesired release in healthy tissue, resulting in good biocompatibility both in vitro and in vivo. The in vitro studies demonstrated that F-ZIF exhibits enhanced efficacy in eradicating fungal pathogens in their biofilm growth state compared with the free fluconazole. Furthermore, in vivo experiments reveal the better effectiveness of F-ZIF in treating Candida albicans-induced vulvovaginal candidiasis, and less infection-related inflammation was observed. Hence, the one-port synthetic F-ZIF presents a promising solution for addressing fungal biofilm-related infections.