The biological fate of the polymer nanocarrier material monomethoxy poly(ethylene glycol)- block-poly(d,l-lactic acid) in rat

Xiangjun Meng; Zhi Zhang; Jin Tong; Hui Sun; John Paul Fawcett; Jingkai Gu

doi:10.1016/j.apsb.2021.02.018

The biological fate of the polymer nanocarrier material monomethoxy poly(ethylene glycol)- block-poly(d,l-lactic acid) in rat

Acta Pharm Sin B. 2021 Apr;11(4):1003-1009. doi: 10.1016/j.apsb.2021.02.018. Epub 2021 Mar 4.

Authors

Xiangjun Meng^{1

2}, Zhi Zhang¹, Jin Tong¹, Hui Sun¹, John Paul Fawcett¹, Jingkai Gu^{1

3}

Affiliations

¹ Research Center for Drug Metabolism, School of Life Sciences, Jilin University, Changchun 130012, China.
² School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
³ Beijing Institute of Drug Metabolism, Beijing 102209, 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.

Keywords: Biodistribution; Excretion; Metabolism; Monomethoxy poly(ethylene glycol)-block-poly(d,l-lactic acid); Nanocarrier material; Pharmacokinetics; Polymer; Rat.