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

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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, K, Tagawa, T, Korenaga, M, Chiba, M, Asai, T, Watanabe, N, Takeoka, S, Handa, M, Ikeda, Y & Oku, N 2011, 'Decoration of fibrinogen γ-chain peptide on adenosine diphosphate-encapsulated liposomes enhances binding of the liposomes to activated platelets', International Journal of Pharmaceutics, vol. 407, no. 1-2, pp. 151-157. https://doi.org/10.1016/j.ijpharm.2011.01.014
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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