Development and Characterization of Optimized Sustained Release Voriconazole-Loaded Chitosan Nanoparticles for Ocular Delivery

Abstract

Voriconazole is an approved antifungal agent belonging to the triazole family. It was generally used for treating aggressive fungal infections such as invasive candidiasis or aspergillosis, as well as certain fungal infections in immunocompromised patients. Voriconazole has an oral bioavailability of 96%, and patients can receive the medication either by oral or parenteral routes. To fabricate a topical ocular voriconazole delivery system, we prepared voriconazole-loaded chitosan nanoparticles by ionic gelation of chitosan with the addition of sodium tripolyphosphate (TPP). Three chitosan polymers with different molecular weights were tested by varying chitosan and TPP concentrations and the produced nanoparticles were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and x-ray powder diffraction (XRD). The obtained data was presented into a Box-Behnken design, which showed the set of optimum parameters that would yield an optimized formulation with the most favorable properties. Subsequently, the optimized formulation was synthesized and voriconazole release from this formulation, and it was monitored over 48 hours. Since the drug-loaded nanoparticles have high drug loading, show no burst effect, and sustain drug release for up to 48 h, this formulation can be a potentially efficient ocular delivery system for voriconazole.