論文

査読有り 国際誌
2022年1月31日

Subvisible Particles Derived by Dropping Stress Enhance Anti-PEG Antibody Production and Clearance of PEGylated Proteins in Mice.

Journal of pharmaceutical sciences
  • Takaki Nakajima
  • ,
  • Kazuya Nagano
  • ,
  • Yuka Fukuda
  • ,
  • Yu Ishima
  • ,
  • Hiroko Shibata
  • ,
  • Ryo Isaka
  • ,
  • Tian-Qi Zhang
  • ,
  • Yuya Haga
  • ,
  • Kazuma Higashisaka
  • ,
  • Hirofumi Tsujino
  • ,
  • Tatsuhiro Ishida
  • ,
  • Akiko Ishii-Watabe
  • ,
  • Yasuo Tsutsumi

111
5
開始ページ
1363
終了ページ
1369
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.xphs.2022.01.023

Bioconjugation with polyethylene glycol (PEG) is important for protein drug development as it has improved biological stability. In contrast, proteins including PEGylated ones are susceptible to physicochemical stresses. Particularly, protein drugs in solution may form aggregates or subvisible particles if they are exposed to dropping stress during transportation. However, many PEGylation studies have focused on its usefulness, such as the extension of half-life in blood, and changes in the physical properties or biological responses of PEGylated proteins under dropping stress remain unexplored. Here, we prepared four PEGylated ovalbumin (PEG-OVA) molecules conjugated with different lengths (5 or 20 kDa) and numbers (large [L] or small [S]) of PEG, analyzed the formation of subvisible particles under dropping stress, and examined their impact on antibody production and clearance. Under dropping stress, the aggregated particle concentration of 20 kDa PEG-OVA (S) and (L) solutions was approximately 3-fold that of the OVA solution. Moreover, administration of 20 kDa PEG-OVA with dropping stress induced anti-PEG antibody production and clearance of PEG-OVA. As a mechanism, dropping stress could enhance the uptake of 20 kDa PEG-OVA (L) by macrophages. These findings could provide insights into proper transportation conditions to ensure the quality of PEGylated protein drugs.

リンク情報
DOI
https://doi.org/10.1016/j.xphs.2022.01.023
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/35108562
ID情報
  • DOI : 10.1016/j.xphs.2022.01.023
  • PubMed ID : 35108562

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