Novel delivery systems for coagulation proteins

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 vit.io half-life (T-1/2) Of 6 weeks at 37 degrees C and is months at 4 degrees C. Upon bolus subcutaneous (SC) injection in animals, hCFIX had a bioavailability of up to 16% compared to intravenous (IV) dose. When delivered by SC 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 SC, gave prolonged plasma levels over those obtained by bolus IV or SC injection. Freeze-dried human coagulation factor Vm (hCFVIII) formulated in non-aqueous solvents had in vitro T-1/2 up to 80 days at 37 degrees C.