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- Title
Accelerated Blood Clearance Phenomenon Upon Repeated Injection of PEG-modified PLA-nanoparticles.
- Authors
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
- Abstract
Abstract Purpose We recently developed prostaglandin E1 (PGE1)-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 PGE1 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.
- Subjects
PROSTAGLANDIN E1; NANOPARTICLES; POLYMERIC drug delivery systems; POLYETHYLENE glycol; TARGETED drug delivery; LABORATORY rats; THERAPEUTICS
- Publication
Pharmaceutical Research, 2009, Vol 26, Issue 10, p2270
- ISSN
0724-8741
- Publication type
Article