Translational Advances in Antifungal Therapy Through Strategic Innovation in Nanocarrier and Targeted Drug Delivery Systems

Abstract

Fungal infections remain a global health issue, particularly for immunocompromised patients. Conventional antifungal agents, such as azoles, polyenes, and echinocandins, are often hampered by limited solubility, systemic toxicity, and inadequate tissue penetration, yielding suboptimal efficacy and fostering drug resistance. In response, drug delivery systems have emerged, offering revolutionary solutions to these issues. This review comprehensively discusses the new generation of advanced antifungal delivery systems, with an emphasis on nanotechnology-based platforms such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, and smart hydrogels. Such platforms have superior efficacy in terms of targeting, controlled release, and reduced toxicity through pharmacokinetic improvement and enhanced biodistribution. Liposomal amphotericin B and SUBA-itraconazole have shown impressive clinical potential, whereas oral amphotericin B cochleates and nano-amphotericin B inhaled for lung infections are under clinical development. Other examples of next-generation localized delivery technologies include enzymesensitive hydrogels and nanocarrier-loaded dressings. Despite this promising translational potential, challenges such as manufacturing scalability, regulatory sophistication, and biological targeting specificity persist. However, interdisciplinary approaches drive advances in antifungal pharmacotherapy, particularly patient-friendly therapies. Integrating mycology and nanomedicine promises a paradigm shift in antifungal treatment, from systemic, toxic regimens to site-specific, durable, responsive therapies.