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Novel delivery systems for coagulation proteins.

S I Miekka·T Jameson·M Singh·C Woolverton·H M Lin·R Krajcik·M MacPhee·W N Drohan
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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.

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Administration, CutaneousAnimalsDrug Delivery SystemsFactor IXHalf-LifeHemophilia AHumansHydrogelsInjections, IntravenousRabbitsJournal Article

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BibTeXRIS

S I Miekka, T Jameson, M Singh, C Woolverton, H M Lin, R Krajcik, M MacPhee, W N Drohan. 1998. Novel delivery systems for coagulation proteins.. https://doi.org/10.1046/j.1365-2516.1998.440436.x

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