Kinetics of Release of Heparin from Alginate Hydrogel

Abstract

Injected sodium alginate may be a useful perivascular drug delivery vehicle. This study was performed to determine the release rates of heparin from sodium alginate hydrogels cross-linked with varying amounts of calcium gluconate. Six hydrogels, composed of 0.16 mEq sodium alginate and 4,000 units unfractionated heparin, were cross-linked with calcium gluconate to yield ion equivalence (IE) ratios (calcium:alginate) of 0.2, 0.4, 0.58, 0.8, 1.0, or 1.2. Two milliliters of normal saline was placed on top of each gel and allowed to remain in contact for up to 10 days. At set time intervals, the amount of heparin in the eluent was determined with use of high-performance liquid chromatography. Gels with 0.2 and 0.4 IE were partially liquid at 24 hours; the other gels solidified within 10 minutes. The 0.58 IE gel was slowest to solidify but immobilized the most heparin and released heparin slowest over 10 days. At 10 days, between 5.5% and 9.8% of the heparin immobilized was retained in the gel. This hydrogel shows promise as a vehicle for in vivo perivascular heparin delivery. The 0.58:1 IE ratio hydrogel has slowest release rate and the greatest immobilization despite its longer cross-linking time.