Development of fibrinogen γ-chain peptide-coated, adenosine diphosphate-encapsulated liposomes as a synthetic platelet substitute

Y. Okamura, S. Takeoka, K. Eto, I. Maekawa, T. Fujie, H. Maruyama, Y. Ikeda, Makoto Handa

研究成果: Article査読

49 被引用数 (Scopus)

抄録

Background: The dodecapeptide HHLGGAKQAGDV (H12), corresponding to the fibrinogen γ-chain carboxy-terminal sequence (γ400-411), is a specific binding site of the ligand for platelet GPIIb/IIIa complex. We have evaluated H12-coated nanoparticles (polymerized albumin or liposome) as platelet function-supporting synthetic products. Objectives: To strengthen the hemostatic ability of H12-coated particles as a platelet substitute, we exploited installation of a drug delivery function by encapsulating adenosine diphosphate (ADP) into liposomes [H12-(ADP)-liposomes]. Methods and results: Via selective interaction with activated platelets through GPIIb/IIIa, H12-(ADP)-liposomes were capable of augmenting agonist-induced platelet aggregation by releasing ADP in an aggregation-dependent manner. When intravenously injected into rats, liposomes were readily targeted to sites of vascular injury as analyzed on computed tomography. In fact, comparable to fresh platelets, liposomes exhibited considerable hemostatic ability for correcting prolonged bleeding time in a busulphan-induced thrombocytopenic rabbit model. In addition, the liposomes showed no activating or aggregating effects on circulating platelets in normal rabbits. Conclusion: H12-(ADP)-liposome may thus offer a promising platelet substitute, being made with only synthetic materials and exerting hemostatic functions in vivo via reinforcement of primary thrombus formation by residual platelets in thrombocytopenia at sites of vascular injury, but not in circulation.

本文言語English
ページ(範囲)470-477
ページ数8
ジャーナルJournal of Thrombosis and Haemostasis
7
3
DOI
出版ステータスPublished - 2009 2 16

ASJC Scopus subject areas

  • Hematology

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