Accelerated blood clearance phenomenon upon repeated injection of peg-modified pla-nanoparticles

Tsutomu Ishihara, Miho Takeda, Haruka Sakamoto, Ayumi Kimoto, Chisa Kobayashi, Naoko Takasaki, Kanae Yuki, Ken Ichiro Tanaka, Mitsuko Takenaga, Rie Igarashi, Taishi Maeda, Naoki Yamakawa, Yoshinari Okamoto, Masami Otsuka, Tatsuhiro Ishida, Hiroshi Kiwada, Yutaka Mizushima, Tohru Mizushima

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Abstract

Purpose: We recently developed prostaglandin E1 (PGE 1)-encapsulated nanoparticles, prepared with a poly(lactide) homopolymer (PLA, Mw∈=∈17,500) and monomethoxy poly(ethyleneglycol)- PLA block copolymer (PEG-PLA) (NP-L20). In this study, we tested whether the accelerated blood clearance (ABC) phenomenon is observed with NP-L20 and other PEG-modified PLA-nanoparticles in rats. Methods: The plasma levels of PGE 1 and anti-PEG IgM antibody were determined by EIA and ELISA, respectively. Results: Second injections of NP-L20 were cleared much more rapidly from the circulation than first injections, showing that the ABC phenomenon was induced. This ABC phenomenon, and the accompanying induction of anti-PEG IgM antibody production, was optimal at a time interval of 7 days between the first and second injections. Compared to NP-L20, NP-L33s that were prepared with PLA (Mw∈=∈28,100) and have a smaller particle size induced production of anti-PEG IgM antibody to a lesser extent. NP-L20 but not NP-L33s gave rise to the ABC phenomenon with a time interval of 14 days. NP-L33s showed a better sustained-release profile of PGE1 than NP-L20. Conclusions: This study revealed that the ABC phenomenon is induced by PEG-modified PLA-nanoparticles. We consider that NP-L33s may be useful clinically for the sustained-release and targeted delivery of PGE1.

Original languageEnglish
Pages (from-to)2270-2279
Number of pages10
JournalPharmaceutical research
Volume26
Issue number10
DOIs
Publication statusPublished - 2009 Oct 1

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Keywords

  • ABC phenomenon
  • Anti-PEG IgM antibody
  • Biodegradable nanoparticles
  • Encapsulation
  • Prostaglandin E

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Ishihara, T., Takeda, M., Sakamoto, H., Kimoto, A., Kobayashi, C., Takasaki, N., Yuki, K., Tanaka, K. I., Takenaga, M., Igarashi, R., Maeda, T., Yamakawa, N., Okamoto, Y., Otsuka, M., Ishida, T., Kiwada, H., Mizushima, Y., & Mizushima, T. (2009). Accelerated blood clearance phenomenon upon repeated injection of peg-modified pla-nanoparticles. Pharmaceutical research, 26(10), 2270-2279. https://doi.org/10.1007/s11095-009-9943-x