Improving the pharmacokinetics and tissue distribution of pyrinezolid by self-assembled polymeric micelles

Antibiotic-resistance by bacteria is a growing global concern within the healthcare field, and it has provided an impetus for continued antimicrobial development. Pyrinezolid (PZ), a novel oxazolidinone compound, can effectively inhibit most gram-positive bacteria, including methicillin-resistant St...

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Bibliographic Details
Published in:Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2017-08, Vol.156, p.149-156
Main Authors: Long, Haiyue, Li, Xiaoling, Sang, Zitai, Mei, Lan, Yang, Tao, Li, Zicheng, Zhou, Liangxue, Zheng, Yu, He, Gu, Guo, Gang, Wang, Zhenling, Deng, Yong, Luo, Youfu
Format: Article
Language:English
Subjects:
Animals
HEK293 Cells
Humans
Male
Mice
Mice, Inbred BALB C
Micelles
Oxazolidinones - pharmacokinetics
Polymers - chemistry
Rats
Rats, Sprague-Dawley
Tissue Distribution
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Summary:Antibiotic-resistance by bacteria is a growing global concern within the healthcare field, and it has provided an impetus for continued antimicrobial development. Pyrinezolid (PZ), a novel oxazolidinone compound, can effectively inhibit most gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Though PZ is a promising antimicrobial candidate, the druggability of PZ is limited by its poor water solubility. Therefore, the amphipathic mPEG-PLLA copolymer was used to prepare the pyrinezolid micelles (PZ-M). Herein, we described the preparation, pharmacokinetic properties, tissue distribution, efficacy and toxicity of PZ-M. In vivo studies show that PZ-M possess prolonged blood circulation time and increased oral bioavailability compared with free PZ. Meanwhile, PZ-M increase lung PZ exposure and reduce liver and kidney exposure, which indicates that PZ-M may enhance the efficacy in vivo in MRSA-related pneumonia patients and decrease potential renal and hepatic toxicities.
ISSN:0927-7765
1873-4367
DOI:10.1016/j.colsurfb.2017.05.014