Accelerated Blood Clearance Phenomenon Upon Repeated Injection of PEG-modified PLA-nanoparticles

作者：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^*

来源：Pharmaceutical Research, 2009, 26(10): 2270-2279.

DOI：10.1007/s11095-009-9943-x

• ABC phenomenon
• anti-PEG IgM antibody
• biodegradable nanoparticles
• encapsulation
• prostaglandin E(1)

We recently developed prostaglandin E(1) (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.
The plasma levels of PGE(1) and anti-PEG IgM antibody were determined by EIA and ELISA, respectively.
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 PGE(1) than NP-L20.
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 PGE(1).

• 出版日期2009-10
• 单位河北医科大学