Thromb Haemost 2005; 93(06): 1061-1068
DOI: 10.1160/TH04-08-0485
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Factor VIII efficient and specific non-covalent binding to PEGylated liposomes enables prolongation of its circulation time and haemostatic efficacy

Moshe Baru
1   Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel
,
Lea Carmel-Goren
1   Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel
,
Yechezkel Barenholz
2   Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel
,
Inbal Dayan
1   Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel
,
Savely Ostropolets
1   Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel
,
Igal Slepoy
1   Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel
,
Nira Gvirtzer
1   Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel
,
Vladimir Fukson
1   Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel
,
Jack Spira
1   Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel
› Author Affiliations
Grant support: This study was partially supported by a grant from the Israel-U. S. Binational Industrial Research and Development (BIRD) Foundation.
Further Information

Publication History

Received 09 August 2004

Accepted after revision 01 March 2005

Publication Date:
11 December 2017 (online)

Summary

Haemophilia A is a bleeding disorder caused by the lack of factor VIII (FVIII). We report the prolongation of exogenous FVIII circulation time and haemostatic efficacy by its formulation with PEGylated liposomes (PEGLip). FVIII binds non-covalently but with high affinity in a specific mode with the external surface of PEGLip neither losing its activity nor its binding to von Willebrand Factor. Experiments in haemophilic and non-haemophilic mice indicate that the circulation time and clotting efficacy of PEGLip-formulated exogenous FVIII (PEGLip-FVIII) are significantly enhanced over those of free FVIII. The data support the feasibility of using PEGLip-FVIII to extend the duration of haemostatic efficacy in the treatment of haemophilia A.

 
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