著者

小出 裕之 浅井 知浩 畑中 剣太朗 清水 広介 横山 昌幸 石田 竜弘 際田 弘志 奥 直人

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.129, no.12, pp.1445-1451, 2009-12-01 (Released:2009-12-01)

参考文献数

21

被引用文献数

10 12

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Liposomes modified with polyethylene glycol (PEG) can stably exist in the bloodstream because the PEG on the liposomes attracts a water shell to the liposomal surface. Since these liposomes are long circulating nanocarriers, they are used as drug and gene delivery tools. Repeat injection of PEGylated liposomes, however, is known to induce the accelerated blood clearance (ABC) phenomenon. In the ABC phenomenon, PEGylated liposomes that are injected subsequent to the first injection are cleared rapidly from the bloodstream and accumulate in the liver, resulting in loss of their long-circulating characteristics. The induction of ABC phenomenon is related to the production of anti-PEG IgM from splenic B cells. To elucidate the mechanism of the phenomenon, we firstly examined the relationship between the induction of ABC phenomenon and the concentration of PEGylated liposomes, and observed that the high dose of those did not induce the phenomenon. Next, we investigated whether polymeric micelles trigger ABC phenomenon or not. Finally, the size-dependency of ABC phenomenon was investigated by use of variously sized PEGylated liposomes and polymeric micelles having PEG chains. Our data suggest that the initiation of ABC phenomenon would be size-dependent, and particles smaller than 30 nm did not induce ABC phenomenon. We anticipate that the elucidation of the ABC phenomenon will be helpful for the development of DDS formulations.

著者

奥 直人 浅井 知浩 清水 広介

出版者

静岡県立大学

雑誌

基盤研究(B)

巻号頁・発行日

2008

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花粉症などのアレルギー疾患では脱感作療法などが行われているが、根本的治療法はない。本研究では、アレルギーの基となる免疫細胞の活性を恒久的に抑える根本的治療法を開発する。すなわち薬物送達システムを利用し、特定の薬物を運ぶキャリアーに抗原を結合することで、抗体産生細胞に特異的にキャリアーを認識させ、特定の細胞のみに薬物を送達し細胞の活性を抑える新たな治療戦略を確立する。