Purpose: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 periadventitial I125-labeled IUdR delivery to suppress intimal hyperplasia following angioplasty in vivo.
Materials and Methods: Four hydrogels, composed of 0.16mEq 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. 2mL of normal saline was
placed on top of each hydrogel and allowed to remain in contact at 37oC
for up to 30days. At set time intervals, the concentration and amount of IUdR
in eluate were assayed by high performance liquid chromatography using UV
detection and Water symmetry C18column.
The data were calculated based on the calibration curve of peak area versus
IUdR concentration. The hydrogel morphologic degradations were also observed.Results: The hydrogel entrapped 92.94%, 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 from3: 1 IE ratio hydrogel decreased faster than that from other hydrogels over time (P<0.001). The 4:1, 5:1 and 6:1 IE ratio hydrogels produced more than 10
M
IUdR concentrations in eluates for 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 IE ratio
hydrogels were very close, however they were lower than that of the 3:1 IE
hydrogel (p<0.001). 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.Conclusions: The sodium alginate hydrogel with 4:1 IE ratio exhibited an optimal IUdR sustained release and degraded faster than the higher IE ratio hydrogels.