Accelerated Blood Clearance Phenomenon Upon Repeated Injection of PEG-modified PLA-nanoparticles |
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Authors: | 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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Institution: | 1. Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, 862-0973, Japan 2. DDS Institute, The Jikei University School of Medicine, Tokyo, 105-8461, Japan 3. Division of Drug Delivery System, Institute of Medical Science, St. Marianna University, Kawasaki, 216-8512, Japan 4. Institute of Health Bioscience, The University of Tokushima, Tokushima, 770-8505, Japan
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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. |
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