Decoration of fibrinogen γ-chain peptide on adenosine diphosphate-encapsulated liposomes enhances binding of the liposomes to activated platelets

Koji Tokutomi, Toshiaki Tagawa, Maki Korenaga, Masatoshi Chiba, Tomohiro Asai, Naohide Watanabe, Shinji Takeoka, Makoto Handa, Yasuo Ikeda, Naoto Oku

    Research output: Contribution to journalArticle

    11 Citations (Scopus)

    Abstract

    For the purpose of efficient hemostasis, we previously developed ADP-encapsulated liposomes modified with a dodecapeptide (HHLGGAKQAGDV, H12), H12-(ADP)Lipo. This liposome actually enhanced platelet aggregation in vitro, and showed significant hemostatic effect in vivo. Since fibrinogen (Fbg) is abundant in the bloodstream, it is unclear why this liposome binds platelets so efficiently, overcoming the competition with Fbg. Therefore, we investigated the relationship between H12 density on the liposome and the binding ability to platelets, and evaluated the inhibitory effect of Fbg on the binding of H12-(ADP)Lipo to platelets. As a result, the binding ability to platelets steeply increased depending on H12 density until it reached about 3 × 1015 H12 molecules/m2. The 50% inhibition concentration of Fbg on the binding of H12-(ADP)Lipo to platelets was about 25-fold over the concentration of H12 molecules on the liposome. Moreover, almost no inhibition by Fbg was observed at the physiological concentration of it. This result suggests that the ability of H12 to bind to GPIIb/IIIa increased overwhelmingly by the anchoring to the liposome that enabled the cooperative binding of H12 peptides to the platelets.

    Original languageEnglish
    Pages (from-to)151-157
    Number of pages7
    JournalInternational Journal of Pharmaceutics
    Volume407
    Issue number1-2
    DOIs
    Publication statusPublished - 2011 Apr 4

    Fingerprint

    Liposomes
    Adenosine Diphosphate
    Fibrinogen
    Blood Platelets
    Peptides
    Hemostatics
    Hemostasis
    Platelet Aggregation

    Keywords

    • ADP
    • Fibrinogen
    • Hemostasis
    • Liposome
    • Platelet aggregation

    ASJC Scopus subject areas

    • Pharmaceutical Science

    Cite this

    Decoration of fibrinogen γ-chain peptide on adenosine diphosphate-encapsulated liposomes enhances binding of the liposomes to activated platelets. / Tokutomi, Koji; Tagawa, Toshiaki; Korenaga, Maki; Chiba, Masatoshi; Asai, Tomohiro; Watanabe, Naohide; Takeoka, Shinji; Handa, Makoto; Ikeda, Yasuo; Oku, Naoto.

    In: International Journal of Pharmaceutics, Vol. 407, No. 1-2, 04.04.2011, p. 151-157.

    Research output: Contribution to journalArticle

    Tokutomi, Koji ; Tagawa, Toshiaki ; Korenaga, Maki ; Chiba, Masatoshi ; Asai, Tomohiro ; Watanabe, Naohide ; Takeoka, Shinji ; Handa, Makoto ; Ikeda, Yasuo ; Oku, Naoto. / Decoration of fibrinogen γ-chain peptide on adenosine diphosphate-encapsulated liposomes enhances binding of the liposomes to activated platelets. In: International Journal of Pharmaceutics. 2011 ; Vol. 407, No. 1-2. pp. 151-157.
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