Purpose: Recently, increasing trend in emergence of infections due to triazole-resistant Aspergillus fumigate has become a major medical concern. According to recent epidemiological research, the prevalence of azole-resistant A. fumigatus has increased remarkably from 3.3 percent to 6.6 percent in Iran. Accordingly, novel antifungal agents/formulations are needed in order to face with the resistant Aspergillus fumigates isolates. We prepared voriconazole-loaded solid lipid nanoparticles (VRC-SLNs) and investigated the efficacy of the optimal formulation on A. fumigatus isolates.
Methods: Voriconazole-loaded solid lipid nanoparticles were prepared using the probe-ultrasonication method. The properties of obtained SLNs were characterized by photon correlation spectroscopy (PCS) for average particle size and zeta potential (at 25 degree and a fixed angle of 90 degree). Morphology was characterized by transmission-electron microscopy. The minimum inhibitory concentrations (MIC) for the new formulations against strains of Aspergillus were investigated using the Clinical and Laboratory Standards Institute document M38-A2 as a guideline on 62 clinical and environmental isolates of A. fumigatus.
Results: The VRC-SLNs presented a spherical shape with a mean diameter and zeta potential of 286.6± 4.7nm and -15 ± 4.1 mV respectively. Using a new formulation of voriconazole led to a significant decrease in MICs for all Aspergillus either VRC-susceptible or VRC-resistant isolates (P < 0.05). The MIC50 drug concentration was obtained as 0.015 μg/ml for both voriconazole-susceptible strains of A. fumigates while it was obtained 0.25 μg/ml against voriconazole (p<0.05). Voriconazole-resistant strains showed MIC50 0.015 μg/ml as well.
Conclusion: In this study, we evaluated a novel delivery system to face with A. fumigatus strains that exhibit different susceptibility to a conventional formulation of VRC. Novel drug formulations may increase the bioavailability and dissolution rate of voriconazole. This study was the first to report the effectiveness of VRC-SLNs as alternative delivery systems for VRC on A. fumigatus isolates.
Full conference title:
- AAA 8th (2018)