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

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)470-477
Number of pages8
JournalJournal of Thrombosis and Haemostasis
Volume7
Issue number3
DOIs
Publication statusPublished - 2009

Fingerprint

Liposomes
Adenosine Diphosphate
Fibrinogen
Blood Platelets
Peptides
Hemostatics
Vascular System Injuries
Rabbits
Busulfan
Bleeding Time
Platelet Aggregation
Thrombocytopenia
Nanoparticles
Albumins
Thrombosis
Binding Sites
Tomography
Ligands
Pharmaceutical Preparations

Keywords

  • ADP
  • Fibrinogen γ-chain peptide
  • Liposomes
  • Platelet substitutes
  • Thrombocytopenic rats and rabbits

ASJC Scopus subject areas

  • Hematology

Cite this

Development of fibrinogen γ-chain peptide-coated, adenosine diphosphate-encapsulated liposomes as a synthetic platelet substitute. / Okamura, Y.; Takeoka, S.; Eto, K.; Maekawa, I.; Fujie, T.; Maruyama, H.; Ikeda, Y.; Handa, Makoto.

In: Journal of Thrombosis and Haemostasis, Vol. 7, No. 3, 2009, p. 470-477.

Research output: Contribution to journalArticle

Okamura, Y. ; Takeoka, S. ; Eto, K. ; Maekawa, I. ; Fujie, T. ; Maruyama, H. ; Ikeda, Y. ; Handa, Makoto. / Development of fibrinogen γ-chain peptide-coated, adenosine diphosphate-encapsulated liposomes as a synthetic platelet substitute. In: Journal of Thrombosis and Haemostasis. 2009 ; Vol. 7, No. 3. pp. 470-477.
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AU - Ikeda, Y.

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AB - 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.

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