Formulation and Characterization of Isavuconazole-Loaded Chitosan/Sodium Alginate Nanoparticles for Dermal Delivery: in Vitro and in Vivo Evaluation for Enhanced Antifungal Therapy

Abstract

The present study aimed to develop isavuconazole-loaded nanoparticles (NPs) using chitosan and sodium alginate polymers via the ionic gelation technique for topical antifungal therapy. Nanoparticles were formulated with various surfactants and extensively characterized for their physicochemical properties. The particle size of the developed NPs ranged from 167 to 475 nm, with a polydispersity index (PDI) between 0.26 ± 0.09 and 0.39 ± 0.23, indicating uniform particle distribution. The zeta potential values confirmed the surface charge variation among formulations: chitosan and chitosan-alginate NPs exhibited a positive charge (33.08 ± 0.86 to 46 ± 2.9 mV), while alginate-only NPs were negatively charged (-30 ± 2.63 mV). Scanning electron microscopy revealed that all nanoparticles were spherical and smooth. The drug content ranged from 81.54 to 90.56%, with a drug loading capacity of 7.4 ± 1.1% to 10.3 ± 1.7%. Entrapment efficiency across formulations F1-F7 varied between 40.21 ± 1.54% and 60.64 ± 1.43%. ATR-FTIR analysis confirmed the compatibility of isavuconazole with chitosan, sodium alginate, and other excipients. The in vitro release profile indicated sustained drug release from the prepared nanoparticles. Kinetic modeling of drug release studies confirmed that the optimized formulation followed the Higuchi model. The skin permeation studies were performed using rat skin and demonstrated gradual and controlled drug transport. The optimized formulation (F4), containing tween 80 as a surfactant and permeation enhancer, showed the highest skin penetration (75.37%) and retention (19.72%). Antifungal activity against Candida albicans was significantly enhanced in the nanoparticle formulation, with F4 exhibiting a zone of inhibition of 17.65 mm compared to the pure drug. In vivo antifungal efficacy using a cutaneous candidiasis model revealed a marked reduction in fungal burden with F4, decreasing to 1.95 log CFU/lesion. Additionally, skin irritation studies indicated no signs of erythema, edema, or inflammation. Therefore, the developed chitosan/sodium alginate nanoparticles could be a promising drug delivery system for the enhancing antifungal efficacy of isavuconazole.