Elucidation of Accelerated Blood Clearance Phenomenon Caused by Repeat Injection of PEGylated Nanocarriers

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  • KOIDE Hiroyuki
    Department of Medical Biochemistry, Graduate School of Pharmaceutical Sciences, University of Shizuoka
  • ASAI Tomohiro
    Department of Medical Biochemistry, Graduate School of Pharmaceutical Sciences, University of Shizuoka
  • HATANAKA Kentaro
    Department of Medical Biochemistry, Graduate School of Pharmaceutical Sciences, University of Shizuoka
  • SHIMIZU Kosuke
    Department of Medical Biochemistry, Graduate School of Pharmaceutical Sciences, University of Shizuoka
  • YOKOYAMA Masayuki
    Medical Engineering Laboratory Research Center for Medical Science, Jikei University School of Medicine
  • ISHIDA Tatsuhiro
    Institute of Health Biosciences, The University of Tokushima
  • KIWADA Hiroshi
    Institute of Health Biosciences, The University of Tokushima
  • OKU Naoto
    Department of Medical Biochemistry, Graduate School of Pharmaceutical Sciences, University of Shizuoka

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Other Title
  • PEG化ナノキャリア頻回投与によるaccelerated blood clearance現象の機構解明
  • PEGカ ナノキャリアヒンカイ トウヨ ニ ヨル accelerated blood clearance ゲンショウ ノ キコウ カイメイ

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Abstract

  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.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 129 (12), 1445-1451, 2009-12-01

    The Pharmaceutical Society of Japan

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