Pharmacokinetic Study of Adenosine Diphosphate-Encapsulated Liposomes Coated with Fibrinogen γ-Chain Dodecapeptide as a Synthetic Platelet Substitute in an Anticancer Drug-Induced Thrombocytopenia Rat Model

Kazuaki Taguchi, Hayato Ujihira, Hiroshi Watanabe, Atsushi Fujiyama, Mami Doi, Shinji Takeoka, Yasuo Ikeda, Makoto Handa, Masaki Otagiri, Toru Maruyama

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    A fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV, H12)-coated, adenosine diphosphate (ADP)-encapsulated liposome [H12-(ADP)-liposome] was designed to achieve optimal performance as a homeostatic agent and expected as a synthetic platelet alternative. For the purpose of efficient function as platelet substitute, H12-(ADP)-liposomes should potentially have both acceptable pharmacokinetic and biodegradable properties under conditions of an adaptation disease including thrombocytopenia induced by anticancer drugs. The aim of this study was to characterize the pharmacokinetics of H12-(ADP)-liposomes in busulphan-induced thrombocytopenic rats using 14C, 3H double radiolabeled H12-(ADP)-liposomes, in which the encapsulated ADP and liposomal membrane (cholesterol) were labeled with 14C and 3H, respectively. After the administration of H12-(ADP)-liposomes, they were determined to be mainly distributed to the liver and spleen and disappeared from organs within 7 days after injection. The encapsulated ADP was mainly eliminated in the urine, whereas the outer membrane (cholesterol) was mainly eliminated in feces. The successive dispositions of the H12-(ADP)-liposomes were similar in both normal and thrombocytopenic rats. However, the kinetics of H12-(ADP)-liposomes in thrombocytopenic rats was more rapid, compared with the corresponding values for normal rats. These findings, which well reflect the clinical features of patients with anticancer drug-induced thrombocytopenia, provide useful information for the development of the H12-(ADP)-liposomes for future clinical use.

    Original languageEnglish
    Pages (from-to)3852-3859
    Number of pages8
    JournalJournal of Pharmaceutical Sciences
    Volume102
    Issue number10
    DOIs
    Publication statusPublished - 2013 Oct

    Fingerprint

    Liposomes
    Thrombocytopenia
    Adenosine Diphosphate
    Fibrinogen
    Blood Platelets
    Pharmacokinetics
    Pharmaceutical Preparations
    Cholesterol
    Busulfan
    Membranes
    Feces
    Reference Values
    Spleen
    Urine
    Injections
    Liver

    Keywords

    • Adenosine-diphosphate
    • Biocompatibility
    • Cancer chemothrapy
    • Disease state
    • Disposition
    • Dodecapeptide
    • Liposome
    • Platelet substitute
    • Thrombocytopenia

    ASJC Scopus subject areas

    • Pharmaceutical Science

    Cite this

    Pharmacokinetic Study of Adenosine Diphosphate-Encapsulated Liposomes Coated with Fibrinogen γ-Chain Dodecapeptide as a Synthetic Platelet Substitute in an Anticancer Drug-Induced Thrombocytopenia Rat Model. / Taguchi, Kazuaki; Ujihira, Hayato; Watanabe, Hiroshi; Fujiyama, Atsushi; Doi, Mami; Takeoka, Shinji; Ikeda, Yasuo; Handa, Makoto; Otagiri, Masaki; Maruyama, Toru.

    In: Journal of Pharmaceutical Sciences, Vol. 102, No. 10, 10.2013, p. 3852-3859.

    Research output: Contribution to journalArticle

    Taguchi, Kazuaki ; Ujihira, Hayato ; Watanabe, Hiroshi ; Fujiyama, Atsushi ; Doi, Mami ; Takeoka, Shinji ; Ikeda, Yasuo ; Handa, Makoto ; Otagiri, Masaki ; Maruyama, Toru. / Pharmacokinetic Study of Adenosine Diphosphate-Encapsulated Liposomes Coated with Fibrinogen γ-Chain Dodecapeptide as a Synthetic Platelet Substitute in an Anticancer Drug-Induced Thrombocytopenia Rat Model. In: Journal of Pharmaceutical Sciences. 2013 ; Vol. 102, No. 10. pp. 3852-3859.
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    abstract = "A fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV, H12)-coated, adenosine diphosphate (ADP)-encapsulated liposome [H12-(ADP)-liposome] was designed to achieve optimal performance as a homeostatic agent and expected as a synthetic platelet alternative. For the purpose of efficient function as platelet substitute, H12-(ADP)-liposomes should potentially have both acceptable pharmacokinetic and biodegradable properties under conditions of an adaptation disease including thrombocytopenia induced by anticancer drugs. The aim of this study was to characterize the pharmacokinetics of H12-(ADP)-liposomes in busulphan-induced thrombocytopenic rats using 14C, 3H double radiolabeled H12-(ADP)-liposomes, in which the encapsulated ADP and liposomal membrane (cholesterol) were labeled with 14C and 3H, respectively. After the administration of H12-(ADP)-liposomes, they were determined to be mainly distributed to the liver and spleen and disappeared from organs within 7 days after injection. The encapsulated ADP was mainly eliminated in the urine, whereas the outer membrane (cholesterol) was mainly eliminated in feces. The successive dispositions of the H12-(ADP)-liposomes were similar in both normal and thrombocytopenic rats. However, the kinetics of H12-(ADP)-liposomes in thrombocytopenic rats was more rapid, compared with the corresponding values for normal rats. These findings, which well reflect the clinical features of patients with anticancer drug-induced thrombocytopenia, provide useful information for the development of the H12-(ADP)-liposomes for future clinical use.",
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    AU - Doi, Mami

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