Kinetics of release of heparin from alginate hydrogel

PURPOSE: Injected sodium alginate may be a useful perivascular drug deliver y vehicle. This study was performed to determine the release rates of hepar in from sodium alginate hydrogels crosslinked with varying amounts of calci um gluconate, MATERIALS AND METHODS: Six hydrogels, composed of 0.16 mEq sodium alginate and 4,000 units unfractionated heparin, were cross-linked with calcium gluc onate 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 highperformance liquid chromatography, RESULTS: Gels with 0.2 and 0.4 IE were partially liquid at 24 hours; the ot her gels solidified within 10 minutes, The 0.58 IE gel was slowest to solid ify but immobilized the most heparin and released heparin slowest over 10 d ays, At 10 days, between 5.5% and 9.8% of the heparin immobilized was retai ned in the gel. CONCLUSION: This hydrogel shows promise as a vehicle for in vivo perivascul ar heparin delivery. The 0.58:1 IE ratio hydrogel has slowest release rate and the greatest immobilization despite its longer cross-linking time.