Fungal infections continue to represent a significant global health challenge, contributing to considerable morbidity and mortality, particularly among immunocompromised patients. The increasing incidence of antifungal resistance has further complicated therapeutic management, requiring the exploration of novel treatment strategies. Posaconazole, a third-generation triazole antifungal, exhibits broad-spectrum activity against resistant pathogens including Candida, Aspergillus, Cryptococcus, and Mucorales. Despite this potential, its clinical application is hindered by poor solubility, variable oral bioavailability, and limited penetration into infection sites. To address these challenges, nanotechnology-based delivery systems have gained attention as innovative approaches to improve the pharmacokinetic and therapeutic performance of posaconazole. This review discusses recent advances in the design and application of nanocarriers, with a particular focus on topical, ocular, vaginal, and systemic routes of administration. Various nanosystems such as liposomes, nanoemulsion, nanosponge, nanostructured lipid carriers, polymeric nanoparticles, micelles, and dendrimers have been investigated for their ability to enhance drug solubility, stability, and site-specific targeting. Topical delivery systems demonstrate improved dermal penetration and sustained release, while vaginal delivery systems provide mucoadhesion and extended retention. Moreover, ocular nanocarriers have shown promise in increasing corneal permeation, residence time, and therapeutic efficacy in fungal keratitis. Collectively, these approaches not only minimize systemic toxicity but also enhance patient compliance and treatment outcomes. Overall, nanocarrier-mediated delivery represents a promising advancement in antifungal therapy, and future studies should prioritize clinical translation, long-term safety assessment, and cost-effectiveness to establish these systems as practical alternatives to conventional formulations.
Gawad et al. (Wed,) studied this question.