Laverde-Rojas Valentina, Liscano Yamil, Rivera-Sánchez Sandra Patricia, Ocampo-Ibáñez Ivan Darío, Betancourt Yeiston, Alhajj Maria José, Yarce Cristhian J, Salamanca Constain H, Oñate-Garzón Jose
Facultad de Salud, Programa de Medicina, Universidad Santiago de Cali, Calle 5 No. 62-00, Cali 760035, Colombia.
Facultad de Ciencias Básicas, Programa de Microbiología, Universidad Santiago de Cali, Calle 5 No. 62-00, Cali 760035, Colombia.
Pharmaceutics. 2020 Dec 30;13(1):41. doi: 10.3390/pharmaceutics13010041.
Colistin is a re-emergent antibiotic peptide used as a last resort in clinical practice to overcome multi-drug resistant (MDR) Gram-negative bacterial infections. Unfortunately, the dissemination of colistin-resistant strains has increased in recent years and is considered a public health problem worldwide. Strategies to reduce resistance to antibiotics such as nanotechnology have been applied successfully. In this work, colistin was characterized physicochemically by surface tension measurements. Subsequently, nanoliposomes coated with highly deacetylated chitosan were prepared with and without colistin. The nanoliposomes were characterized using dynamic light scattering and zeta potential measurements. Both physicochemical parameters fluctuated relatively to the addition of colistin and/or polymer. The antimicrobial activity of formulations increased by four-fold against clinical isolates of susceptible but did not have antimicrobial activity against multidrug-resistant (MDR) bacteria. Interestingly, the free coated nanoliposomes exhibited the same antibacterial activity in both sensitive and MDR strains. Finally, the interaction of colistin with phospholipids was characterized using molecular dynamics (MD) simulations and determined that colistin is weakly associated with micelles constituted by zwitterionic phospholipids.
黏菌素是一种重新出现的抗生素肽,在临床实践中作为克服多重耐药(MDR)革兰氏阴性菌感染的最后手段使用。不幸的是,近年来耐黏菌素菌株的传播有所增加,被认为是全球范围内的一个公共卫生问题。诸如纳米技术等减少抗生素耐药性的策略已成功应用。在这项工作中,通过表面张力测量对黏菌素进行了物理化学表征。随后,制备了有和没有黏菌素的、包覆有高度脱乙酰化壳聚糖的纳米脂质体。使用动态光散射和zeta电位测量对纳米脂质体进行了表征。这两个物理化学参数都相对于黏菌素和/或聚合物的添加而波动。制剂对敏感临床分离株的抗菌活性提高了四倍,但对多重耐药(MDR)细菌没有抗菌活性。有趣的是,游离的包覆纳米脂质体在敏感菌株和MDR菌株中均表现出相同的抗菌活性。最后,使用分子动力学(MD)模拟对黏菌素与磷脂的相互作用进行了表征,并确定黏菌素与两性离子磷脂构成的胶束弱相关。