Novel platelet substitutes

Disk-shaped biodegradable nanosheets and their enhanced effects on platelet aggregation

Yosuke Okamura, Yoshihito Fukui, Koki Kabata, Hidenori Suzuki, Makoto Handa, Yasuo Ikeda, Shinji Takeoka

    Research output: Contribution to journalArticle

    25 Citations (Scopus)

    Abstract

    We have studied biocompatible spherical carriers carrying a dodecapeptide, HHLGGAKQAGDV (H12), on their surface as platelet substitutes. This peptide is a fibrinogen γ-chain carboxy-terminal sequence (γ400-411) and specifically recognizes the active form of glycoprotein IIb/IIIa on activated platelets. Our purpose is to assess the possibility of making a novel platelet substitute consisting of disk-shaped nanosheets having a large contact area for the targeting site, rather than conventional small contact area spherical carriers. The H12 peptide was conjugated to the surface of the free-standing nanosheets made of biodegradable poly(D,L-lactide-co-glycolide) (PLGA). These H12-PLGA nanosheets were fabricated onto 3 μm disk-shaped patterned hydrophobic octadecyl regions on a SiO2 substrate. By way of comparison, spherical H12-PLGA microparticles with the same surface area and conjugation number of H12 were also prepared. The resulting H12-PLGA nanosheets specifically interacted with the activated platelets adhered on the collagen surface at twice the rate of the H12-PLGA microparticles under flow conditions, and showed platelet thrombus formation in a two-dimensional spreading manner. Thus, H12-PLGA nanosheets might be a suitable candidate novel platelet alternative substitute for infused human platelet concentrates for the treatment of bleeding in patients with severe thrombocytopenia.

    Original languageEnglish
    Pages (from-to)1958-1965
    Number of pages8
    JournalBioconjugate Chemistry
    Volume20
    Issue number10
    DOIs
    Publication statusPublished - 2009 Oct 21

    Fingerprint

    Nanosheets
    Platelets
    Platelet Aggregation
    Blood Platelets
    Agglomeration
    Peptides
    Glycoproteins
    Platelet Glycoprotein GPIIb-IIIa Complex
    polylactic acid-polyglycolic acid copolymer
    Collagen
    Thrombocytopenia
    Fibrinogen
    Thrombosis
    Hemorrhage
    Substrates

    ASJC Scopus subject areas

    • Biotechnology
    • Bioengineering
    • Organic Chemistry
    • Pharmaceutical Science
    • Biomedical Engineering
    • Pharmacology

    Cite this

    Novel platelet substitutes : Disk-shaped biodegradable nanosheets and their enhanced effects on platelet aggregation. / Okamura, Yosuke; Fukui, Yoshihito; Kabata, Koki; Suzuki, Hidenori; Handa, Makoto; Ikeda, Yasuo; Takeoka, Shinji.

    In: Bioconjugate Chemistry, Vol. 20, No. 10, 21.10.2009, p. 1958-1965.

    Research output: Contribution to journalArticle

    Okamura, Yosuke ; Fukui, Yoshihito ; Kabata, Koki ; Suzuki, Hidenori ; Handa, Makoto ; Ikeda, Yasuo ; Takeoka, Shinji. / Novel platelet substitutes : Disk-shaped biodegradable nanosheets and their enhanced effects on platelet aggregation. In: Bioconjugate Chemistry. 2009 ; Vol. 20, No. 10. pp. 1958-1965.
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