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

doi:10.1016/j.apsb.2021.02.018

. 2021 Apr;11(4):1003-1009.

doi: 10.1016/j.apsb.2021.02.018. Epub 2021 Mar 4.

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

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.

PMID: 33996412
PMCID: PMC8105770
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

Xiangjun Meng et al. Acta Pharm Sin B. 2021 Apr.

. 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.

PMID: 33996412
PMCID: PMC8105770
DOI: 10.1016/j.apsb.2021.02.018

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.

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Figures

**Figure 1**
Mean plasma concentration-time curve of PEG-PLA after a single intravenous injection of 37.5 mg/kg PEG-PLA to rat (data are mean ± SD, n = 6).

**Figure 2**
The biodistribution of PEG-PLA in rat at 0.25, 4 and 36 h after a single intravenous injection of 37.5 mg/kg PEG-PLA (data are mean ± SD, n = 6).

**Figure 3**
Mean cumulative excretion‒time curve for PEG-PLA in rat bile after a single intravenous injection of 37.5 mg/kg PEG-PLA (data are mean ± SD, n = 7).

**Figure 4**
Application of the MS^ALL technique to the detection of PEG produced by metabolism of PEG-PLA in rat urine. (A) Total ion chromatogram; (B) extracted ion chromatograms of PEG showing PEG characteristic fragment ions at m/z 133.08 and 177.11; and (C) the mass spectrum of PEG.

**Figure 5**
(A) Chromatogram of a blank rat urine sample spiked with PEG 2000 at 50 μg/mL showing extracted fragment ions at 133.08 ± 0.01 Da (blue) and 177.11 ± 0.01 Da (red) and (B) the mass spectrum of PEG 2000.

**Figure 6**
Mean cumulative excretion‒time curves of PEG in (A) rat urine (n = 6) and (B) bile (n = 7) after a single intravenous injection of 37.5 mg/kg PEG-PLA (data are mean ± SD).

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References

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[1] Su H., Wang Y., Liu S., Wang Y., Liu Q., Liu G. Emerging transporter-targeted nanoparticulate drug delivery systems. Acta Pharm Sin B. 2019;9:49–58. - PMC - PubMed

[2] Su H., Wang Y., Liu S., Wang Y., Liu Q., Liu G. Emerging transporter-targeted nanoparticulate drug delivery systems. Acta Pharm Sin B. 2019;9:49–58. - PMC - PubMed

[3] Zhao Q.H., Qiu L.Y. An overview of the pharmacokinetics of polymer-based nanoassemblies and nanoparticles. Curr Drug Metab. 2013;14:832–839. - PubMed

[4] Zhao Q.H., Qiu L.Y. An overview of the pharmacokinetics of polymer-based nanoassemblies and nanoparticles. Curr Drug Metab. 2013;14:832–839. - PubMed

[5] Wang A.Z., Langer R., Farokhzad O.C. Nanoparticle delivery of cancer drugs. Annu Rev Med. 2012;63:185–198. - PubMed

[6] Wang A.Z., Langer R., Farokhzad O.C. Nanoparticle delivery of cancer drugs. Annu Rev Med. 2012;63:185–198. - PubMed

[7] Liu G.W., Prossnitz A.N., Eng D.G., Cheng Y., Subrahmanyam N., Pippin J.W. Glomerular disease augments kidney accumulation of synthetic anionic polymers. Biomaterials. 2018;178:317–325. - PubMed

[8] Liu G.W., Prossnitz A.N., Eng D.G., Cheng Y., Subrahmanyam N., Pippin J.W. Glomerular disease augments kidney accumulation of synthetic anionic polymers. Biomaterials. 2018;178:317–325. - PubMed

[9] Li J., Burgess D.J. Nanomedicine-based drug delivery towards tumor biological and immunological microenvironment. Acta Pharm Sin B. 2020;10:2110–2124. - PMC - PubMed

[10] Li J., Burgess D.J. Nanomedicine-based drug delivery towards tumor biological and immunological microenvironment. Acta Pharm Sin B. 2020;10:2110–2124. - PMC - PubMed

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

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

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