title: Factor VIII efficient and specific non-covalent binding to PEGylated liposomes enables prolongation of its circulation time and haemostatic efficacy.
abstract: 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.
authors.affiliation: Omri Laboratories Ltd., Bldg. 22, Weizmann Science Park, Nes-Ziona, P.O. Box 619, Rehovot 76106, Israel. moshe@omrilabs.co.il
authors.forename: Moshe
authors.initials: M
authors.lastname: Baru
authors.forename: Lea
authors.initials: L
authors.lastname: Carmel-Goren
authors.forename: Yechezkel
authors.initials: Y
authors.lastname: Barenholz
authors.forename: Inbal
authors.initials: I
authors.lastname: Dayan
authors.forename: Savely
authors.initials: S
authors.lastname: Ostropolets
authors.forename: Igal
authors.initials: I
authors.lastname: Slepoy
authors.forename: Nira
authors.initials: N
authors.lastname: Gvirtzer
authors.forename: Vladimir
authors.initials: V
authors.lastname: Fukson
authors.forename: Jack
authors.initials: J
authors.lastname: Spira
mesh_terms: D000818:Animals; D005169:Factor VIII / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D008081:Liposomes; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D005169:Factor VIII