Therapeutic efficacy of pegylated polymyxin E in the treatment of infection induced by gramnegative bacteria and the effect of reducing nephrotoxicity / 药学学报
Acta Pharmaceutica Sinica
; (12): 605-612, 2015.
Article
in Zh
| WPRIM
| ID: wpr-257093
Responsible library:
WPRO
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.
Full text:
1
Index:
WPRIM
Main subject:
Pharmacology
/
Polyethylene Glycols
/
Cell Line
/
Chemistry
/
Colistin
/
Cell Biology
/
Drug Therapy
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Escherichia coli
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Escherichia coli Infections
/
Toxicity
Limits:
Animals
/
Humans
Language:
Zh
Journal:
Acta Pharmaceutica Sinica
Year:
2015
Type:
Article