Hemostatic effects of polymerized albumin nano-particles carrying fibrinogen g-chain dodecapeptide as platelet substitutes

POLY 481

Yosuke Okamura, y.okamura@ruri.waseda.jp1, Toshinori Fujie2, Makoto Handa3, Yasuo Ikeda3, and Shinji Takeoka, takeoka@waseda.jp4. (1) Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1, Ohkubo, Shinjuku-ku, Tokyo, 169-8555, Japan, (2) Department of Life Science and Medical Bioscience, Graduate School of Science and Engineering, Waseda University, 3-4-1, Ohkubo, Shinjuku-ku, Tokyo, 169-8555, Japan, (3) Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo, 169-8582, (4) Department of Applied Chemistry, Faculty of Science and Engineering, Waseda University, 3-4-1, Ohkubo, Shinjuku, Tokyo, 169-8555, Japan
We have focused on a dodecapeptide, HHLGGAKQAGDV (H12), which is specific for fibrinogen g-chain carboxy-terminal sequence (g400-411) as a recognition site of a platelet substitute. In this paper, we conjugated H12 to the surface of a polymerized albumin nanoparticle (H12-polyAlb) as a biocompatible carrier to produce a particle having hemostatic ability, and evaluated in vitro and in vivo effects as a platelet substitute. When thrombocytopenic blood in the presence of H12-polyAlb (f260±60 nm)) was flowed on the collagen-plate, the surface coverage of DiOC6-labeled platelets was increased to 3.9±1.1 % from 2.1±0.4 % in the absence of H12-polyAlb, indicating that H12-polyAlb enhanced platelet thrombus formation. The bleeding times of normal rats ([platelet]=8.1±0.9x105> /mL) or thrombocytopenic rats ([platelet]=2.0±0.3x105> /mL) were 187±51 and 609±153 s, respectively. H12-polyAlb administration at a dose of 4 mg/kg significantly shortened the bleeding time to 342±73 s, whereas polyAlb did not show any effects (553±104 s). These results indicate that H12-polyAlb would be a suitable candidate for an alternative to human platelet concentrates.
 

Nanoparticles and Microparticles: Synthesis and Applications
6:00 PM-8:00 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster

Division of Polymer Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006