TY - JOUR
T1 - Accelerated blood clearance phenomenon upon repeated injection of peg-modified pla-nanoparticles
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
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Health, Labour, and Welfare of Japan, as well as the Japan Science and Technology Agency and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
PY - 2009/10
Y1 - 2009/10
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.
AB - 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.
KW - ABC phenomenon
KW - Anti-PEG IgM antibody
KW - Biodegradable nanoparticles
KW - Encapsulation
KW - Prostaglandin E
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U2 - 10.1007/s11095-009-9943-x
DO - 10.1007/s11095-009-9943-x
M3 - Article
C2 - 19633820
AN - SCOPUS:69949132111
VL - 26
SP - 2270
EP - 2279
JO - Pharmaceutical Research
JF - Pharmaceutical Research
SN - 0724-8741
IS - 10
ER -