Release abilities of adenosine diphosphate from phospholipid vesicles with different membrane properties and their hemostatic effects as a platelet substitute

Yosuke Okamura, Shunsuke Katsuno, Hidenori Suzuki, Hitomi Maruyama, Makoto Handa, Yasuo Ikeda, Shinji Takeoka

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

We have constructed phospholipid vesicles with hemostatic activity as a platelet substitute. The vesicles were conjugated with a dodecapeptide (HHLGGAKQAGDV, H12), which is a fibrinogen γ-chain carboxy-terminal sequence (γ400-411). We have recently exploited these vesicles as a potential drug delivery system by encapsulation of adenosine 5'-diphosphate (ADP) (H12-(ADP)-vesicles). Here we explore the relationship between the ADP release from H12-(ADP)-vesicles with different membrane properties and their hemostatic effects. In total, we prepared five kinds of H12-(ADP)-vesicles with different lamellarities and membrane flexibilities. By radioisotope-labeling, we directly show that H12-(ADP)-vesicles were capable of augmenting platelet aggregation by releasing ADP in an aggregation-dependent manner. The amount of ADP released from the vesicles was dependent on their membrane properties. Specifically, the amount of ADP released increased with decreasing lamellarity and tended to increase with increasing membrane flexibility. Our in vivo results clearly demonstrated that H12-(ADP)-vesicles with the ability to release ADP exert considerable hemostatic action in terms of correcting prolonged bleeding time in a busulphan-induced thrombocytopenic rat model. We propose a recipe to control the hemostatic abilities of H12-(ADP)-vesicles by modulating ADP release based on membrane properties. We believe that this concept will be invaluable to the development of platelet substitutes and other drug carriers.

Original languageEnglish
Pages (from-to)373-379
Number of pages7
JournalJournal of Controlled Release
Volume148
Issue number3
DOIs
Publication statusPublished - 2010 Dec 20

Keywords

  • Adenosine 5'-diphosphate (ADP)
  • Controlled release
  • Lamellarity
  • Membrane flexibility
  • Phospholipid vesicles
  • Platelet substitute

ASJC Scopus subject areas

  • Pharmaceutical Science

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