Antifungal efficacy of Itraconazole loaded PLGA-nanoparticles stabilized by vitamin-E TPGS: In vitro and ex vivo studies

Abstract

Itraconazole (ITZ) loaded Poly-(D, L-lactic-co-glycolic acid, PLGA) nanoparticles (PLGA-NPs) stabilized by D-α-Tocopherol polyethylene-glycol succinate-1000 (TPGS) were developed by nanoprecipitation and single emulsion solvent evaporation methods to improve antifungal activity of ITZ by enhancing its solubility, and hence bioavailability. Encapsulation efficiency, drug loading, in-vitro release, ex-vivo permeation and antifungal activity were performed for the optimized PLGA-NPs. Characterization of PLGA-NPs were performed by scanning electron microscopy, dynamic light scattering, differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffractometry. We observed that nanoprecipitation method was more efficient in encapsulating ITZ by using 0.3% TPGS (stabilizer) than single emulsion solvent evaporation method. Our thermal analysis studies showed no characteristic peaks for crystalline ITZ, indicating drug efficiently encapsulated inside the nanoparticle with no compatibility issues. Drug loaded PLGA-NPs preserved the antifungal activity of ITZ against Candida albicans. Drug release profile from the NPs showed an initial burst release followed by an extended release phase suggesting the potential of NPs for sustained release applications. Furthermore, ITZ encapsulated in PLGA-NPs showed enhanced intestinal permeability in the ex-vivo study. In conclusion, the developed nano-system successfully encapsulated ITZ, yielding an increased permeation and consequential antifungal activity.