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

Research output: Contribution to journalArticle

115 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Nanoparticles
Polyethylene glycols
Alprostadil
Blood
Injections
Immunoglobulin M
Antibodies
Homopolymerization
Particle Size
Antibody Formation
Rats
Enzyme-Linked Immunosorbent Assay
Particle size
Plasmas
anti-IgM
monomethoxypolyethyleneglycol-polylactide block copolymer

Keywords

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

ASJC Scopus subject areas

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

Cite this

Ishihara, T., Takeda, M., Sakamoto, H., Kimoto, A., Kobayashi, C., Takasaki, N., ... 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

Accelerated blood clearance phenomenon upon repeated injection of peg-modified pla-nanoparticles. / Ishihara, Tsutomu; Takeda, Miho; Sakamoto, Haruka; Kimoto, Ayumi; Kobayashi, Chisa; Takasaki, Naoko; Yuki, Kanae; Tanaka, Ken Ichiro; Takenaga, Mitsuko; Igarashi, Rie; Maeda, Taishi; Yamakawa, Naoki; Okamoto, Yoshinari; Otsuka, Masami; Ishida, Tatsuhiro; Kiwada, Hiroshi; Mizushima, Yutaka; Mizushima, Tohru.

In: Pharmaceutical Research, Vol. 26, No. 10, 10.2009, p. 2270-2279.

Research output: Contribution to journalArticle

Ishihara, T, Takeda, M, Sakamoto, H, Kimoto, A, Kobayashi, C, Takasaki, N, Yuki, K, Tanaka, KI, 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, vol. 26, no. 10, pp. 2270-2279. https://doi.org/10.1007/s11095-009-9943-x
Ishihara, Tsutomu ; Takeda, Miho ; Sakamoto, Haruka ; Kimoto, Ayumi ; Kobayashi, Chisa ; Takasaki, Naoko ; Yuki, Kanae ; Tanaka, Ken Ichiro ; Takenaga, Mitsuko ; Igarashi, Rie ; Maeda, Taishi ; Yamakawa, Naoki ; Okamoto, Yoshinari ; Otsuka, Masami ; Ishida, Tatsuhiro ; Kiwada, Hiroshi ; Mizushima, Yutaka ; Mizushima, Tohru. / Accelerated blood clearance phenomenon upon repeated injection of peg-modified pla-nanoparticles. In: Pharmaceutical Research. 2009 ; Vol. 26, No. 10. pp. 2270-2279.
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AU - Ishihara, Tsutomu

AU - Takeda, Miho

AU - Sakamoto, Haruka

AU - Kimoto, Ayumi

AU - Kobayashi, Chisa

AU - Takasaki, Naoko

AU - Yuki, Kanae

AU - Tanaka, Ken Ichiro

AU - Takenaga, Mitsuko

AU - Igarashi, Rie

AU - Maeda, Taishi

AU - Yamakawa, Naoki

AU - Okamoto, Yoshinari

AU - Otsuka, Masami

AU - Ishida, Tatsuhiro

AU - Kiwada, Hiroshi

AU - Mizushima, Yutaka

AU - Mizushima, Tohru

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N2 - 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.

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KW - ABC phenomenon

KW - Anti-PEG IgM antibody

KW - Biodegradable nanoparticles

KW - Encapsulation

KW - Prostaglandin E

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