State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology & Toxicology, Beijing 100850, China.
Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China.
Int J Pharm. 2019 Jan 10;554:284-291. doi: 10.1016/j.ijpharm.2018.11.029. Epub 2018 Nov 13.
Antimicrobial peptides (AMPs) are regarded as next-generation antibiotics to replace conventional antibiotics due to their rapid and broad-spectrum antimicrobial properties and far less sensitivity to the development of pathogen resistance. However, they are susceptible to proteolysis in vivo by endogenous or bacterial proteases as well as induce the lysis of red blood cells, which prevent their intravenous applications. In this work, polyion complex (PIC) micelles of the cationic AMP MSI-78 and the anionic copolymer methoxy poly(ethylene glycol)-b-poly(α-glutamic acid) (mPEG-b-PGlu) were prepared to develop novel antimicrobial agents for potential application in vivo. With an increase in molar ratio of mPEG-b-PGlu to MSI-78, the complexation ability of the PIC micelles increased. FITC-labeled MSI-78 showed a sustained release from the PIC micelles. More importantly, these PIC micelles greatly decreased the hemolytic toxicity of MSI-78 to human red blood cells, without influencing its antimicrobial activity. Thus, this approach could be used as a suitable in vivo delivery method of AMPs in the future.
抗菌肽 (AMPs) 因其快速广谱的抗菌特性和对病原体耐药性发展的敏感性低，被视为替代传统抗生素的下一代抗生素。然而，它们在体内容易被内源性或细菌蛋白酶水解，并且会诱导红细胞破裂，这阻止了它们的静脉应用。在这项工作中，制备了阳离子 AMP MSI-78 和阴离子共聚物甲氧基聚（乙二醇）-b-聚（α-谷氨酸）（mPEG-b-PGlu）的聚离子复合物（PIC）胶束，以开发新型抗菌剂，用于潜在的体内应用。随着 mPEG-b-PGlu 与 MSI-78 的摩尔比增加，PIC 胶束的复合能力增加。FITC 标记的 MSI-78 从 PIC 胶束中持续释放。更重要的是，这些 PIC 胶束大大降低了 MSI-78 对人红细胞的溶血毒性，而不影响其抗菌活性。因此，该方法将来可用于 AMPs 的体内递药。
