Prolonged hemostatic ability of polyethylene glycol-modified polymerized albumin particles carrying fibrinogen gamma-chain dodecapeptide.
BACKGROUND
Second-generation platelet (PLT) substitutes for treatment of bleeding were studied and the focus was on a dodecapeptide, HHLGGAKQAGDV (H12), which is a fibrinogen gamma-chain carboxy-terminal sequence (gamma 400-411) and exists only in a fibrinogen domain.


METHODS
H12 was conjugated to the surface of polymerized albumin particles (polyAlb) modified with polyethylene glycol (PEG) chains to produce biocompatible particles (H12-PEG-polyAlb) that had prolonged blood circulation t((1/2)) and were more stable in vitro and in vivo compared with H12-polyAlb (not modified with PEG). H12-PEG-polyAlb was administered intravenously into thrombocytopenic rats and the t((1/2)) of the particles and the tail bleeding time were measured to evaluate the prolongation in the hemostatic effect.


RESULTS
H12-PEG-polyAlb particles modified with PEG prolonged the t((1/2)) and maintained specific binding ability to activated PLTs. The particles dose dependently shortened the tail bleeding time of thrombocytopenic rats 6 hours after injection.


CONCLUSIONS
H12-PEG-polyAlb may be a suitable candidate for treatment of bleeding into thrombocytopenic patients as an alternative to PLT concentrate transfusion.
Okamura
Yosuke
Y
Department of Applied Chemistry, Graduate School of Science and Engineering, Waseda University, Tokyo, Japan.
Fujie
Toshinori
T
Maruyama
Hitomi
H
Handa
Makoto
M
Ikeda
Yasuo
Y
Takeoka
Shinji
S
D000418:Albumins / Q000627:therapeutic use*; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets; D005340:Fibrinogen / Q000627:therapeutic use*; D006207:Half-Life; D006470:Hemorrhage / Q000188:drug therapy; D006490:Hemostatics / Q000737:chemistry* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D051381:Rats; D013921:Thrombocytopenia / Q000628:therapy
D000418:Albumins; D006490:Hemostatics; D010446:Peptide Fragments; D011092:Polyethylene Glycols; D005340:Fibrinogen