title: [Therapeutic efficacy of pegylated polymyxin E in the treatment of infection induced by gramnegative bacteria and the effect of reducing nephrotoxicity].
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.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Xin-xin
authors.initials: XX
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Gan
authors.forename: Na
authors.initials: N
authors.lastname: Wu
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Zhu
authors.forename: Shu-fang
authors.initials: SF
authors.lastname: He
authors.forename: Hui
authors.initials: H
authors.lastname: Ltu
mesh_terms: D000818:Animals; D002460:Cell Line; D003091:Colistin / Q000494:pharmacology* / Q000633:toxicity; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D011092:Polyethylene Glycols; D003091:Colistin