An appraisal of antifungal impacts of nano-liposome containing voriconazole on voriconazole-resistant Aspergillus flavus isolates as a groundbreaking drug delivery system

摘要

Background: This study is an attempt to investigate the effect of nano-liposome containing voriconazole on voriconazole-resistant A. flavus strains on the one hand, and to consider the expression of cyp51A and MDR1genes, regarded as important genes involved in the development of resistance to triazoles before and after voriconazole and voriconazole-loaded nano-liposomes exert their effects, on the other hand.Methods: Strains of A. flavus isolated from patients were investigated and their susceptibility to voriconazole was determined. Next, having applied a slight modification to the thin film hydration-sonication technique, the liposomal formulation of voriconazole was produced. After that, the voriconazole-loaded nano-liposome was subjected to in-vitro antifungal susceptibility testing to obtain minimum inhibitory concentration against fungal isolates. Cyp51A and MDR1 mRNA levels were amplified by qRT-PCR instrument.Results: The effect of nano-liposome containing voriconazole on the reduction of MIC in A. flavus isolates were considered to be significant. After using MIC50 concentration of VCZ, the cyp51A gene expression in voriconazole-susceptible A. flavus strains and voriconazole-resistant strains 10folds and 7folds depicted a downregulation, respectively, which was more pronounced in the expression of a liposomal formulation of VCZ (13folds and 15folds respectively). Identically, the same procedure was applied to MDR1, even though it induced 1, 2, 3, 4-fold reductions.Conclusion: Considering the benefits of liposome-containing voriconazole formulation, such as the reduction of the side effects of the pure drug as well as minimizing the drug's toxicity coupled with the enhanced drug bioavailability and stability, the formulation can be used in drug-sensitive and drug-resistant species.