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

Abstract

Background: Fluconazole (FLZ), a potent antifungal medication, is characterized by poor water solubility that reduced its antifungal efficacy.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: The antifungal activity of FLZ against C. albicans was enhanced markedly via its loading in the alginate/chitosan-based polymeric matrix of NP4.

Keywords: Fluconazole; encapsulation; fungal infection; nanoparticles; particle size; polymer..