Premium
Novel delivery systems for coagulation proteins
Author(s) -
Lee C. A.,
Kessler C. M.,
Varon D.,
Martinowitz U.,
Heim M.,
MIEKKA S. I.,
JAMESON T.,
SINGH M.,
WOOLVERTON C.,
LIN H.M.,
KRAJCIK R.,
MACPHEE M.,
DROHAN W. N.
Publication year - 1998
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1046/j.1365-2516.1998.440436.x
Subject(s) - bolus (digestion) , medicine , haemophilia , clotting factor , bioavailability , coagulation , fibrinogen , chitosan , in vitro , factor ix , pharmacology , subcutaneous injection , chromatography , surgery , chemistry , biochemistry
Summary. 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°C and 18 months at 4°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 VIII (hCFVIII) formulated in non‐aqueous solvents had in vitro T 1/2 up to 80 days at 37°C.