title: Development of fibrinogen gamma-chain peptide-coated, adenosine diphosphate-encapsulated liposomes as a synthetic platelet substitute.
abstract: BACKGROUND
  The dodecapeptide HHLGGAKQAGDV (H12), corresponding to the fibrinogen gamma-chain carboxy-terminal sequence (gamma 400-411), 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.
  
  
  OBJECTIVE
  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].
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okamura
authors.forename: S
authors.initials: S
authors.lastname: Takeoka
authors.forename: K
authors.initials: K
authors.lastname: Eto
authors.forename: I
authors.initials: I
authors.lastname: Maekawa
authors.forename: T
authors.initials: T
authors.lastname: Fujie
authors.forename: H
authors.initials: H
authors.lastname: Maruyama
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: M
authors.initials: M
authors.lastname: Handa
mesh_terms: D000244:Adenosine Diphosphate / Q000008:administration & dosage*; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets; D002214:Capsules / Q000737:chemistry / Q000627:therapeutic use; D020099:Coated Materials, Biocompatible; D016503:Drug Delivery Systems / Q000379:methods*; D005340:Fibrinogen / Q000008:administration & dosage*; D006470:Hemorrhage / Q000188:drug therapy; D006487:Hemostasis / Q000187:drug effects*; D008081:Liposomes / Q000008:administration & dosage*; D053758:Nanoparticles; D011817:Rabbits; D051381:Rats; D013921:Thrombocytopenia / Q000188:drug therapy
chemical_list: D002214:Capsules; D020099:Coated Materials, Biocompatible; D008081:Liposomes; C027539:fibrinopeptides gamma; D000244:Adenosine Diphosphate; D005340:Fibrinogen