| Despite the growing trends in the number of patients at risk for invasive fungal infections, management
with current antifungal agents results in complications due to changes in the epidemiology and drug
susceptibility of invasive fungal infections. In the present research fluconazole-loaded nanostructured
lipid carriers were prepared using probe ultrasonication techniques and investigated the efficacy of the
optimal formulation on a large number of Candida species. The morphology of the obtained
nanostructured lipid carriers was characterized by transmission-electron microscopy. The minimum
inhibitory concentrations (MIC) for the new formulations against strains of Candida were investigated
using the Clinical and Laboratory Standards Institute document M27-A3 and M27-S4 as a guideline. The
fluconazole-loaded nanostructured lipid carriers presented a spherical shape with a mean diameter, zeta
potential and entrapment efficiency of 126.4 15.2 nm, 35.1 3.0 mV, and 93.6 3.5%, respectively. The
drug release from fluconazole-loaded nanostructured lipid carriers exhibited burst-release behavior at
the initial stage followed by sustained release over 24 h. Using a new formulation of fluconazole led to a
significant decrease in MICs for all Candida groups (P < 0.05). Furthermore, C. albicans isolates showed
more susceptibility to fluconazole-loaded nanostructured lipid carriers than C. glabrata and C. parapsilosis
(P < 0.05). The MIC50 drug concentration was obtained as 0.0625, 0.031 and 0.25mg/ml for fluconazoleresistant
strains of C. albicans, C. glabrata, and C. parapsilosis, respectively. In conclusion, a novel delivery
system which can be used as part of a strategy to improve the antifungal activity of fluconazole against
various Candida strains with different susceptibilities to conventional formulations of fluconazole was
evaluated. |