Visualization of liposomes carrying fibrinogen gamma-chain dodecapeptide accumulated to sites of vascular injury using computed tomography.
We have constructed liposomes with hemostatic activity as a platelet substitute using moderately thrombocytopenic rats. The liposomes were conjugated with the dodecapeptide (HHLGGAKQAGDV: H12), which is a fibrinogen gamma-chain C-terminal sequence (gamma 400-411). To visualize liposome accumulation at the site of vascular injury by in vivo computed tomography, a water-soluble contrast dye, N,N'-bis[2-hydroxy-1-(hydroxylmethyl)ethyl]-5-[(2S)-2-hydroxylpropanoylamino]-2,4,6-triiodoisophthalamide (iopamidol), was encapsulated into the H12-conjugated liposomes. We achieved direct visualization of specific accumulation of the H12-(iopamidol)liposomes at the jugular vein injured by ferric chloride and succeeded in semiquantitative analyses of the accumulated amount of H12-liposomes in the injured site. We therefore propose that H12-liposomes that are specifically recruited to, and exert their hemostatic activity at the site of vascular injury, have a significant potential as a carrier and/or as an ideal platelet substitute. Furthermore, the H12-(iopamidol)liposomes would also be clinically useful as diagnostic agents for pathological thrombus detection and as contrast dyes for hepatosplenography.


BACKGROUND
The authors have constructed liposomes with hemostatic activity as a platelet substitute using moderately thrombocytopenic rats. They propose that H12-liposomes that are specifically recruited to, and exert their hemostatic activity at the site of vascular injury, have a significant potential as a carrier and/or as an ideal platelet substitute. Furthermore, the H12-(iopamidol) liposomes would also be clinically useful as diagnostic agents for thrombus detection and as contrast dyes for hepatosplenography.
Okamura
Yosuke
Y
Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, TWIns, Tokyo, Japan.
Eto
Kaoruko
K
Maruyama
Hitomi
H
Handa
Makoto
M
Ikeda
Yasuo
Y
Takeoka
Shinji
S
D000792:Angiography / Q000379:methods*; D000818:Animals; D003287:Contrast Media / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry*; D007142:Immunoglobulin gamma-Chains / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D051381:Rats; D013921:Thrombocytopenia / Q000000981:diagnostic imaging*
D003287:Contrast Media; D004337:Drug Carriers; D007142:Immunoglobulin gamma-Chains; D008081:Liposomes; D010455:Peptides; D005340:Fibrinogen