Development of Zinc Oxide Nanocomposites for Enhanced Antifungal Delivery of Amphotericin B in Systemic Mycoses

Amphotericin B (APB) is a broad‐spectrum antifungal drug, but its clinical use is restricted by dose‐dependent toxicity and formulation‐related problems. The present study aimed to develop and characterize an antifungal delivery system based on a nanocomposite of APB, polyethylene glycol, and zinc oxide (APB–PEG–ZnO NC) with improved in vitro performance as a nanocarrier. ZnO nanoparticles (NPs) were synthesized using a green approach with Eichhornia crassipes leaf extract and subsequently incorporated into an APB–PEG–ZnO NC formulation. The formulation was characterized for particle size, polydispersity index, zeta potential, surface morphology, elemental composition, functional group interactions, crystalline structure, encapsulation efficiency, drug loading, and in vitro drug release. Antifungal activity was evaluated against fungal pathogens, including Candida albicans ( C. albicans ), Aspergillus fumigatus , and Cryptococcus neoformans ( C. neoformans ). The APB–PEG–ZnO NC formulation exhibited enhanced antifungal activity with reduced minimum inhibitory concentration (MIC) values as compared to free APB against all tested fungal species, including 0.026 ± 0.002 µg/mL against C. albicans . This formulation exhibited 1.6% ± 0.2% drug loading, 83.1% ± 3.9% encapsulation efficiency, and a sustained APB release profile compared to APB–PEG and ZnO–APB formulations. These results indicate that APB–PEG–ZnO NCs could be a potential NC‐based platform for APB delivery against systemic fungal infections.