期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 554, 期 -, 页码 284-291出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2018.11.029
关键词
Cationic antimicrobial peptide; MSI-78; Methoxy poly(ethylene glycol)-b-poly(alpha-glutamic acid); Polyion complex micelles; Hemolytic toxicity
资金
- National Natural Science Foundation of China [51373080]
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(alpha-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.
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