Effect of Repeated Injections of Adenosine Diphosphate-Encapsulated Liposomes Coated with a Fibrinogen γ-Chain Dodecapeptide Developed as a Synthetic Platelet Substitute on Accelerated Blood Clearance in a Healthy and an Anticancer Drug-Induced Thrombocytopenia Rat Model

Kazuaki Taguchi, Mai Hashimoto, Shigeru Ogaki, Hiroshi Watanabe, Shinji Takeoka, Yasuo Ikeda, Makoto Handa, Masaki Otagiri, Toru Maruyama

    Research output: Contribution to journalArticle

    2 Citations (Scopus)

    Abstract

    Adenosine diphosphate (ADP)-encapsulated liposomes coated with a fibrinogen γ-chain dodecapeptide [H12 (dodecapeptide (<sup>400</sup>HHLGGAKQAGDV<sup>411</sup>))-(ADP)-liposome] is a synthetic platelet substitute, in which the surface is covered with polyethylene glycol (PEG). It has been reported that repeated injections of PEGylated liposomes induce an accelerated blood clearance (ABC) phenomenon, which involves a loss in the long-circulation half-life of the material when administered repeatedly to the same animals. The objective of this study was to determine whether the ABC phenomenon was induced by repeated injections of H12-(ADP)-liposome in healthy and anticancer drug-induced thrombocytopenia model rats. The findings show that the ABC phenomenon was induced by healthy rats that were repeatedly injected with H12-(ADP)-liposomes at the interval of 5 days at a dose of 10 mg lipids/kg. The ABC phenomenon involves the production of anti-H12-(ADP)-liposome immunoglobulin M (IgM) and complement activation. On the other hand, when thrombocytopenia model rats were repeatedly injected with H12-(ADP)-liposomes under the same conditions, no ABC phenomenon, nor was any suppression of anti-H12-(ADP)-liposome IgM-mediated complement activation observed. We thus conclude that the repeated injection of H12-(ADP)-liposome treatment in rat model with anticancer drug-induced thrombocytopenia did not induce the ABC phenomenon.

    Original languageEnglish
    Pages (from-to)3084-3091
    Number of pages8
    JournalJournal of Pharmaceutical Sciences
    Volume104
    Issue number9
    DOIs
    Publication statusPublished - 2015 Sep 1

    Keywords

    • accelerated blood clearance phenomenon
    • adenosine-diphosphate
    • clearance
    • disposition
    • dodecapeptide
    • liposome
    • pegylation
    • pharmacokinetics
    • platelet substitute
    • thrombocytopenia

    ASJC Scopus subject areas

    • Pharmaceutical Science

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