Biodegradable Polymers-based Nanoparticles to Enhance the Antifungal Efficacy of Fluconazole against Candida albicans.

Abstract

Fluconazole (FLZ), a potent antifungal medication, is characterized by poor water solubility that reduced its antifungal efficacy. This study aimed to prepare FLZ-loaded polymeric nanoparticles (NPs) by using different polymers and techniques as a method of enhancing the antifungal activity of FLZ. NP1, NP2, and NP3 were prepared by the double emulsion/solvent evaporation method using PLGA, PCL, and PLA, respectively. The ionotropic pre-gelation technique was applied to prepare an alginate/chitosan-based formulation (NP4). Particle size, zeta potential, encapsulation efficiency, and loading capacity were characterized. FT-IR spectra of FLZ, the polymers, and the prepared NPs were estimated. NP4 was selected for further in-vitro release evaluation. The broth dilution method was used to assess the antifungal activity of NP4 using a resistant clinical isolate of Candida albicans. The double emulsion method produced smaller-sized particles (<390 nm) but with much lower encapsulation efficiency (<12%). Alternatively, the ionic gelation method resulted in nanosized particles with a markedly higher encapsulation efficiency of about 40%. The FT-IR spectroscopy confirmed the loading of the FLZ molecules in the polymeric network of the prepared NPs. The release profile of NP4 showed a burst initial release followed by a controlled pattern up to 24 hours with a higher percent released relative to the free FLZ suspension. NP4 was able to reduce the value of MIC of FLZ by 20 times. The antifungal activity of FLZ against C. albicans was enhanced markedly via its loading in the alginate/chitosan-based polymeric matrix of NP4.