Department of Microbiology, Guilan University of Medical Sciences, Rasht, Iran.
Department of Microbiology, Islamic Azad University, Tehran Medical Branch, Tehran, Iran.
J Biomed Mater Res A. 2021 Jun;109(6):966-980. doi: 10.1002/jbm.a.37086. Epub 2020 Aug 31.
In the current study, niosome-encapsulated tobramycin based on Span 60 and Tween 60 was synthesized and its biological efficacies including anti-bacterial, anti-efflux, and anti-biofilm activities were investigated against multidrug resistant (MDR) clinical strains of Pseudomonas aeruginosa. The niosomal formulations were characterized using scanning electron microscopy, transmission electron microscopy, and dynamic light scattering measurement. The encapsulation efficiency was found to be 69.54% ±; 0.67. The prepared niosomal formulations had a high storage stability to 60 days with small changes in size and drug entrapment, which indicates that it is a suitable candidate for pharmaceutical applications. The results of biological study showed the anti-bacterial activity via reduction of antibiotic resistance, enhanced anti-efflux and anti-biofilm activities by more folds in comparison to free tobramycin. In addition, niosome encapsulated tobramycin down-regulated the MexAB-OprM efflux genes, pslA and pelA biofilm related genes in MDR P. aeruginosa strains. The anti-proliferative activity of formulation was evaluated against HEK293 cell lines, which exhibited negligible cytotoxicity against HEK293 cells. The finding of our study shows that encapsulation of tobramycin in niosome enhanced the antibacterial activity and reduced antibiotic resistance in MDR strains of P. aeruginosa comparing to free tobramycin and it can be considered as a favorable drug delivery system.
在当前的研究中,合成了基于 Span 60 和 Tween 60 的奈脂质体包裹妥布霉素,并研究了其针对多药耐药(MDR)铜绿假单胞菌临床株的抗菌、抗外排和抗生物膜活性等生物学功效。使用扫描电子显微镜、透射电子显微镜和动态光散射测量对奈脂质体制剂进行了表征。包封效率为 69.54%±0.67。制备的奈脂质体制剂在 60 天内具有很高的储存稳定性,粒径和药物包封率只有微小变化,这表明它是一种适合药物应用的候选药物。生物研究结果表明,与游离妥布霉素相比,通过降低抗生素耐药性、增强抗外排和抗生物膜活性,奈脂质体包裹妥布霉素具有更强的抗菌活性。此外,奈脂质体包裹妥布霉素下调了 MDR 铜绿假单胞菌菌株中的 MexAB-OprM 外排基因、pslA 和 pelA 生物膜相关基因。还评估了制剂对 HEK293 细胞系的抗增殖活性,结果表明该制剂对 HEK293 细胞几乎没有细胞毒性。我们的研究结果表明,与游离妥布霉素相比,奈脂质体包裹妥布霉素可增强抗菌活性并降低 MDR 铜绿假单胞菌菌株的抗生素耐药性,可被视为一种有利的药物传递系统。