Time to overcome fluconazole resistant Candida isolates: Solid lipid nanoparticles as a novel antifungal drug delivery system

Abstract

Antifungal therapy results in complications in management due to changes in the patterns of epidemiology and drug susceptibility of invasive fungal infections. In this study, we prepared fluconazole-loaded solid lipid nanoparticles (FLZ-SLNs) and investigated the efficacy of the optimal formulation on fluconazole (FLZ)-resistant strains of several Candida species. FLZ-SLN was produced using probe ultrasonication techniques. The morphology of the obtained SLNs was characterized by field emission scanning electron microscopy. The minimum inhibitory concentrations for the new formulations against fluconazole-resistant strains of Candida were investigated using CLSI document M27-A3. The FLZ-SLNs presented a spherical shape with a mean diameter, zeta potential and entrapment efficiency of 84.8 nm, -25 mV and 89.6%, respectively. The drug release from FLZ-SLNs exhibited burst release behaviour at the initial stage (the first 30 min) followed by a sustained release over 24h FLZ-resistant yeast strains behaved as susceptible strains after treatment with FLZ-SLNs (<= 8 mu g/ml). The MIC50 drug concentrations were 2 mu g/ml, 1 mu g/ml and 2 mu g/ml for FLZ-resistant strains of Candida albicans, Candida parapsilosis and Candida glabrata, respectively. In this study, we evaluated novel delivery systems for combating Candida strains that exhibit low susceptibility against the conventional formulation of FLZ as a first-line treatment. (C) 2016 Elsevier B.V. All rights reserved.