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

Moshe Baru; Lea Carmel-Goren; Yechezkel Barenholz; Inbal Dayan; Savely Ostropolets; Igal Slepoy; Nira Gvirtzer; Vladimir Fukson; Jack Spira

doi:10.1160/TH04-08-0485

Thrombosis and Haemostasis, Inhaltsverzeichnis

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

¹Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel

,

Lea Carmel-Goren

¹Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel

,

Yechezkel Barenholz

²Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel

,

Inbal Dayan

¹Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel

,

Savely Ostropolets

¹Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel

,

Igal Slepoy

¹Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel

,

Nira Gvirtzer

¹Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel

,

Vladimir Fukson

¹Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel

,

Jack Spira

¹Omri Laboratories Ltd., Nes-Ziona, Rehovot, Israel

› Institutsangaben

Abstract

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.

Keywords

Factor VIII - haemophilia A - haemophilia therapy

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Referenzen

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