Kinetics of iododeoxyuridine release from sodium alginate hydrogel in vitro

Objective: To investigate the kinetics of Iododeoxyuridine (IUdR)release from sodium alginate hydrogel cross-linked with varying amounts of calcium chloride, and to optimize sustained release for further periadventitial I¹²⁵-labeled IUdR delivery to suppress intimal hyperplasia following angioplasty in vivo. Methods: Four hydrogels, com posed of 0.16 mEq sodium alginate and 200 g IUdR, were cross-linked with calcium chloride to yield ion equivalence (IE) ratios (Calcium: alginate) of 3:1, 4:1, 5:1, or 6:1. 2 ml of normal saline was placed on top of each hydrogel and allowed to remain in contact at 37°C for up to 30 days. At set time intervals, the concentration and amount of IUdR in the eluate were assayed by high performance liquid chromatography using UV detection and Water symmetry C18 column. The data for accumulated release rate and concentration in the eluate were calculated based on the calibration curve of peak area versus IUdR concentration. The hydrogel morphologic degradations were also observed. Results: The hydrogels entrapped 92.9%, 98.6%, 98.4% and 98.6% of the IUdR with 3:1, 4:1, 5:1 and 6:1 IE ratios, respectively. IUdR concentration in eluates from 3:1 IE ratio hydrogel decreased faster than that from other hydrogels over time (P < 0.01). The 4:1, 5:1 and 6:1 IE ratio hydrogels produced more than 10 μm IUdR concentrations in eluates for the first 8 days, while the 3:1 IE ratio hydrogel for 4 days. IUdR release rates of the 4:1, 5:1 and 6:1 EE ratio hydrogels were very close, however they were lower than that of the 3:1 IE hydrogel in the first 48 hours (P < 0.05). At day 30, the 3:1 and 4:1 IE ratio hydrogels had 100% and 88% degradation, but no significant degradation was observed in the other hydrogels. Conclusion: The sodium alginate hydrogel with 4:1 IE ratio exhibited an optimal IUdR sustained release and almost complete degradation in 30 days.