Original articles
Xiangjun Meng, Zhi Zhang, Jin Tong, Hui Sun, John Paul Fawcett, Jingkai Gu. The biological fate of the polymer nanocarrier material monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid) in rat[J]. Acta Pharmaceutica Sinica B, 2021, 11(4): 1003-1009

The biological fate of the polymer nanocarrier material monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid) in rat
Xiangjun Menga,c, Zhi Zhanga, Jin Tonga, Hui Suna, John Paul Fawcetta, Jingkai Gua,b
a Research Center for Drug Metabolism, School of Life Sciences, Jilin University, Changchun 130012, China;
b Beijing Institute of Drug Metabolism, Beijing 102209, China;
c School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China
Abstract:
Monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-PLA) is a typical amphiphilic di-block copolymer widely used as a nanoparticle carrier (nanocarrier) in drug delivery. Understanding the in vivo fate of PEG-PLA is required to evaluate its overall safety and promote the development of PEG-PLA-based nanocarrier drug delivery systems. However, acquiring such understanding is limited by the lack of a suitable analytical method for the bioassay of PEG-PLA. In this study, the pharmacokinetics, biodistribution, metabolism and excretion of PEG-PLA were investigated in rat after intravenous administration. The results show that unchanged PEG-PLA is mainly distributed to spleen, liver, and kidney before being eliminated in urine over 48 h mainly (>80%) in the form of its PEG metabolite. Our study provides a clear and comprehensive picture of the in vivo fate of PEG-PLA which we anticipate will facilitate the scientific design and safety evaluation of PEG-PLA-based nanocarrier drug delivery systems and thereby enhance their clinical development.
Key words:    Monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid)    Polymer    Nanocarrier material    Pharmacokinetics    Biodistribution    Metabolism    Excretion    Rat   
Received: 2020-11-01     Revised: 2020-12-23
DOI: 10.1016/j.apsb.2021.02.018
Funds: This work was supported by the National Natural Science Foundation of China (Grant Nos. 81872831 and 82030107) and the National Science and Technology Major Projects for significant new drugs creation of the 13th five-year plan (2017ZX09101001 and 2018ZX09721002007, China).
Corresponding author: Jingkai Gu, gujk@jlu.edu.cn     Email:gujk@jlu.edu.cn
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Xiangjun Meng
Zhi Zhang
Jin Tong
Hui Sun
John Paul Fawcett
Jingkai Gu

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