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

研究成果: Article査読

5 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)3852-3859
ページ数8
ジャーナルJournal of Pharmaceutical Sciences
102
10
DOI
出版ステータスPublished - 2013 10
外部発表はい

ASJC Scopus subject areas

  • Pharmaceutical Science

フィンガープリント 「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」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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