Solid lipid nanoparticles is an effective carrier system to improve delivery of voriconazole to Aspergillus fumigates

M Moazeni1, 2, HR Kelidari3, T Shokohi1, 2, M Nabili4, A Nokhodchi5, 6

Author address: 

1Medical Mycology and Parasitology , School of Medicine,Mazandaran University of Medical Sciences, Sari, Iran 2Invasive Fungi Research Center, MazandMazandaran University of Medical Sciencesaran University, Sari, Iran 3Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran 4Department of Medical Laboratory Sciences, Sari Branch , Islamic Azad University, Sari, Iran 5Pharmaceutics Research Laboratory, School of Life Sciences, University of Sussex, Brighton , United Kingdom 6Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract: 

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.

2018

Full conference title: 

The 8th Advances Against Aspergillus, Lisbon Conference Center, Lisbon, Portugal
    • AAA 8th (2018)