title: Novel delivery systems for coagulation proteins.
abstract: Long-term haemophilia prophylaxis with clotting factors administered by alternative delivery modes requires stable liquid formulations of these factors. We developed an aqueous-formulated human coagulation factor IX (hCFIX) with in vitro half-life (T 1/2) of 6 weeks at 37 degrees C and 18 months at 4 degrees C. Upon bolus subcutaneous (s.c.) injection in animals, hCFIX had a bioavailability of up to 16% compared to intravenous (i.v.) dose. When delivered by s.c. implanted pumps, hCFIX attained > 2% of normal human levels in the animal plasma. Hydrogels of hCFIX in a chitosan derivative, N,O-carboxymethyl chitosan (NOCC), released hCFIX slowly in vitro, and when injected s.c., gave prolonged plasma levels over those obtained by bolus i.v. or s.c. injection. Freeze-dried human coagulation factor VIII (hCFVIII) formulated in non-aqueous solvents had in vitro T 1/2 up to 80 days at 37 degrees C.
authors.affiliation: Jerome H. Holland Laboratory, American Red Cross, Rockville, MD 20855, USA. miekka@usa.redcross.org
authors.forename: S I
authors.initials: SI
authors.lastname: Miekka
authors.forename: T
authors.initials: T
authors.lastname: Jameson
authors.forename: M
authors.initials: M
authors.lastname: Singh
authors.forename: C
authors.initials: C
authors.lastname: Woolverton
authors.forename: H M
authors.initials: HM
authors.lastname: Lin
authors.forename: R
authors.initials: R
authors.lastname: Krajcik
authors.forename: M
authors.initials: M
authors.lastname: MacPhee
authors.forename: W N
authors.initials: WN
authors.lastname: Drohan
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D016503:Drug Delivery Systems; D005164:Factor IX / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D020100:Hydrogels; D007275:Injections, Intravenous; D011817:Rabbits
chemical_list: D020100:Hydrogels; D005164:Factor IX