Formulation and Development of Spray-Dried Atorvastatin Nanoparticles for Potential Antifungal Applications

Background: Atorvastatin (ATR), traditionally prescribed as an antihyperlipidemic agent, has shown promising therapeutic potential beyond its primary indication, including anti-inflammatory, antioxidant, and antifungal properties. However, its clinical application is limited by poor solubility and low bioavailability. Methods: To address these limitations, ATR-loaded nanoparticles were prepared using Gelucire ® 44/14 and Gelucire 50/13 at ratios of 1:1 and 1:3 through spray-drying. The formulations were evaluated for particle size, zeta potential, encapsulation efficiency, solubility, morphology, dissolution, and antifungal activity against four fungal strains of clinical relevance. Results: Increasing the Gelucire ratio from 1:1 to 1:3 significantly reduced particle size (227.30 ± 4.1 to 150.71 ± 3.8 nm) and improved encapsulation efficiency, reaching 83.53%. Dissolution was markedly enhanced, with ATR-GR 44/14 (1:3) achieving nearly complete release within 5 hours. Morphological analysis confirmed the formation of uniformly dispersed nanoparticles. Importantly, antifungal assays demonstrated that ATR-GR 44/14 (1:3) exhibited superior activity against multiple fungal strains compared with other formulations and pure ATR. Conclusions: Spray-dried ATR-GR nanoparticles offer an effective strategy to overcome solubility barriers while enhancing antifungal efficacy. These findings support their potential as a repurposed therapeutic platform for fungal infections and justify further preclinical and clinical investigation, including future exploration of these spray-dried systems as candidates for inhaled antifungal delivery.