Therapeutic efficacy of pegylated polymyxin E in the treatment of infection induced by gramnegative bacteria and the effect of reducing nephrotoxicity.
- Author:
Tao ZHANG
;
Xin-xin ZHANG
;
Yong GAN
;
Na WU
;
Jing-jing ZHU
;
Shu-fang HE
;
Hui LTU
- Publication Type:Journal Article
- MeSH:
Animals;
Cell Line;
Colistin;
pharmacology;
toxicity;
Escherichia coli;
drug effects;
Escherichia coli Infections;
drug therapy;
Humans;
Kidney;
cytology;
drug effects;
Mice;
Polyethylene Glycols;
chemistry
- From:
Acta Pharmaceutica Sinica
2015;50(5):605-612
- CountryChina
- Language:Chinese
-
Abstract:
Polymyxin E shows effective treatment of the infection induced by resistant gramnegative bacteria, but its nephrotoxicity severely limits the clinical application of this drug. In this work, methoxypolyethylene glycols 2000 (mPEG2K)-polymyxin E (PME) was synthesized via chemical grafting reaction and had been characterized. The antimicrobial activity and cytotoxicity of mPEG2K-PME in vitro were investigated on Escherichia coli and HK-2 cells, separately. Intra-abdominal infection model was further established in order to study the therapeutic effect and the toxic effect on kidney of mice. The results showed that mPEG2K-PME exhibited significant inhibitory effect on Escherichia coli and had a lower toxicity on HK-2 cells in vitro. At the same time, mPEG2K-PME had a good efficacy in the treatment of Escherichia coli infected mice in vivo. Moreover, nephrotoxicity caused by mPEG2K-PME was significantly reduced compared to free PME. mPEG2K-PME is promising in development of new preparations with high efficiency and low toxicity.
