Long‐Acting Amphotericin‐B BSA Nanoparticles for Systemic Fungal Infection

Abstract Systemic fungal infections pose a significant therapeutic challenge due to the toxicity and limited efficacy of existing Amphotericin B (AmB) formulations. This study aimed to develop a long‐circulating polymeric nanoparticulate system using bovine serum albumin (BSA) for improved systemic delivery of AmB. BSA nanoparticles were synthesized via the desolvation method and characterized for size (96.1 ± 2.30 nm), surface charge (zeta potential −22.9 ± 1 mV) and drug entrapment efficiency (46.35 ± 6.4%). The formulation exhibited a biphasic drug release pattern, with a 36% initial burst followed by sustained release up to 72.5% over 50 h. In vivo pharmacokinetic studies showed enhanced circulation time, with a 24.2% increase in AUC and an MRT of 55.52 h, compared to 51.25 h for the marketed liposomal formulation. Organ distribution analysis indicated reduced tissue accumulation, while hematological and nephrotoxicity studies confirmed safety upon intravenous administration. The in vivo antifungal assay demonstrated comparable or superior efficacy to existing formulations. These findings suggest that by leveraging surface charge and particle size, BSA nanoparticles offer a promising, cost‐effective alternative for systemic AmB delivery. Further studies are warranted to explore this platform's long‐term safety, scalability, and clinical applicability.