Isik Mehmet, Tan Jeremy P K, Ono Robert J, Sanchez-Sanchez Ana, Mecerreyes David, Yang Yi Yan, Hedrick James L, Sardon Haritz
POLYMAT, University of the Basque Country UPV/EHU Joxe Mari Korta Center, Avda. Tolosa 72, 20018, Donostia-San, Sebastián, Spain.
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore, 138669, Singapore.
Macromol Biosci. 2016 Sep;16(9):1360-7. doi: 10.1002/mabi.201600090. Epub 2016 Jun 8.
There is a growing interest in modern healthcare to develop systems able to fight antibiotic resistant bacteria. Antimicrobial cationic biodegradable polymers able to mimic antimicrobial peptides have shown to be effective against both Gram-positive and Gram-negative bacteria. In these systems, the hydrophilic-hydrophobic ratio and the cationic charge density play a pivotal role in defining the killing efficiency. Nevertheless, many of these antimicrobial polymers show relatively low selectivity as defined by the relative toxicity to mammalian cells or hemolysis relative to pathogens. In this study, a series of polycarbonates containing pendant quaternary ammoniums are used to understand the role of different counter-anions including chloride, citrate, malonate, benzoate, acetate, lactate and trifluoroacetate, and the antibiotic penicillin on antimicrobial efficacy and selectivity. Interestingly, it is found that in spite of the strong antimicrobial activity of trifluoroacetate and benzoate anions, they prove to be much less hemolytic than chloride anion. It is believed that the proper selection of the anion could enhance the potential of antimicrobial polymers to fight against clinically relevant pathogenic infections, while concurrently mitigating harmful side effects.
现代医疗保健领域对于开发能够对抗抗生素耐药细菌的系统的兴趣与日俱增。能够模拟抗菌肽的抗菌阳离子可生物降解聚合物已被证明对革兰氏阳性菌和革兰氏阴性菌均有效。在这些系统中，亲水 - 疏水比和阳离子电荷密度在确定杀菌效率方面起着关键作用。然而，许多这类抗菌聚合物相对于病原体而言，对哺乳动物细胞的相对毒性或溶血作用所定义的选择性较低。在本研究中，使用了一系列含有季铵侧基的聚碳酸酯来了解不同抗衡阴离子（包括氯离子、柠檬酸根离子、丙二酸根离子、苯甲酸根离子、乙酸根离子、乳酸根离子和三氟乙酸根离子）以及抗生素青霉素对抗菌效果和选择性的作用。有趣的是，发现尽管三氟乙酸根离子和苯甲酸根离子具有很强的抗菌活性，但它们的溶血作用比氯离子阴离子小得多。据信，适当选择阴离子可以增强抗菌聚合物对抗临床相关致病性感染的潜力，同时减轻有害的副作用。
