This study aimed to assess the effect of voriconazole (VCZ)-loaded nano-liposomes on biological activity and expression of ERG11, CDR1, and CDR2 genes in fluconazole (FCZ)-resistant Candida albicans. In this study, 5 resistant isolates of C. albicans and 3 susceptible clinical isolates to FCZ were scrutinized from 60 patients suspected of candidiasis. The liposomal formulation of VCZ was produced. After that, the minimum biofilm inhibitory concentration (MBIC) testing was performed and the percentage of growth inhibition was determined. Finally, ERG11, CDR1, and CDR2 mRNA levels were amplified by the quantitative reverse transcription PCR (qRT-PCR) instrument. The obtained results unveiled that VCZ-loaded nano-liposome reduction of minimum inhibitory concentration in C. albicans isolates was remarkable. The results of the MBIC in the most optimum inhibitory concentration of VCZ-loaded nano-liposome were determined to be 4.54 and 4.88 μg/mL for susceptible isolate and resistant isolate, respectively. The ERG11 gene expression in FCZ-resistant C. albicans strains in VCZ-treated, liposomal formulation of VCZ-treated, and nontreated specimens stood at 91%, 63%, and 100%, respectively. Expression levels of CDR1 genes in FCZ-resistant C. albicans were shown to be 91%, 88%, and 100%, respectively. Concerning CDR2 genes, this rate varied to 91%, 78%, and 100% in FCZ resistant, respectively. What our study unveiled was that the use of liposomal VCZ formulation could further reduce the expression of azole-resistant genes compared to VCZ itself. In addition, thanks to more efficacious penetration of the liposomal form, the rate of growth inhibition was considerably higher.

中文翻译：

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负载伏立康唑的纳米脂质体对氟康唑耐药的白色念珠菌临床分离株、生物学活性和 ERG11、CDR1 和 CDR2 基因表达的抗真菌作用

本研究旨在评估负载伏立康唑 (VCZ) 的纳米脂质体对耐氟康唑 (FCZ) 的白色念珠菌的生物活性和ERG11 、 CDR1和CDR2基因表达的影响。在这项研究中，从 60 名疑似念珠菌病患者中仔细检查了 5 株白色念珠菌耐药株和 3 株对 FCZ 敏感的临床分离株。制备了VCZ的脂质体制剂。之后，进行最小生物膜抑制浓度 (MBIC) 测试并确定生长抑制百分比。最后， ERG11 、 CDR1和CDR2通过定量逆转录PCR（qRT-PCR）仪器扩增mRNA水平。获得的结果表明，负载VCZ的纳米脂质体在白色念珠菌分离物中的最低抑制浓度降低是显着的。载有VCZ的纳米脂质体的最佳抑菌浓度MBIC对敏感菌和耐药菌的抑制浓度分别为4.54和4.88 μg/mL。在 VCZ 处理、VCZ 处理的脂质体制剂和未处理的标本中，抗 FCZ 的白色念珠菌菌株中的ERG11基因表达分别为 91%、63% 和 100%。FCZ抗性白色念珠菌中CDR1基因的表达水平分别显示为 91%、88% 和 100%。关于CDR2基因，该比率在 FCZ 抗性中分别变化为 91%、78% 和 100%。我们的研究揭示的是，与 VCZ 本身相比，使用脂质体 VCZ 制剂可以进一步降低唑类抗性基因的表达。此外，由于脂质体形式的更有效渗透，生长抑制率显着提高。