Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies

Abstract

This review highlights the integration of drug repurposing and nanotechnology-driven delivery strategies as innovative approaches to enhance the antifungal activity of statins against mucosal candidiasis, providing a framework for future translational research and clinical application. The rising prevalence of antifungal resistance and virulence factors of Candida albicans underscore the limitations of current therapies. Statins, commonly used as lipid-lowering agents, have emerged as attractive repurposed drug candidates due to their ability to interfere with fungal ergosterol biosynthesis and Ras-mediated signaling pathways. However, repurposed statins face major translational barriers, including poor water solubility, limited mucosal bioavailability, and dose-dependent systemic toxicity. Nanotechnology-driven delivery platforms offer versatile solutions to these challenges, enabling site-directed delivery, improved stability, enhanced permeability, and controlled release. Lipid and polymeric nanocarriers, particularly chitosan-based nanoparticles, enable controlled release and prolonged mucosal retention, making them suitable for localized antifungal therapy. This review explores the integration of statin repurposing with advanced drug delivery strategies as a novel therapeutic paradigm for mucosal candidiasis. Updated evidence demonstrating the antifungal potential of nano-formulated statins is summarized, in conjunction with a general overview of design aspects relevant to optimizing delivery systems. Although still in early stages of investigation, this synergistic approach holds promise for overcoming resistance mechanisms and reducing the recurrence rates associated with existing antifungals. Ultimately, leveraging drug repurposing alongside nanotechnology may accelerate the translation of statin-based antifungal therapies into clinical practice, providing an innovative and cost-effective avenue to broaden the therapeutic arsenal against mucosal Candida infections.