Strontium release system based on alginate for bone tissue engineering: gelation time effect

OBERTI T; CORTIZO AM; TORRES ML; FERNANDEZ JM

Mar del Plata

Congreso; LXI reunión anual de la sociedad argentina de investigación clínica (SAIC), LXIV reunión anual de la sociedad argentina de inmunología (SAI); 2016

Alginate (Alg) is a natural, water-soluble, polysaccharide obtained from brown algae. Due to many attractive features such as good biocompatibility, low toxicity as well as ease of hydrogel formation with divalent cations, it has been widely used in biomedical application. Strontium ranelate (SR) is an orally administered antiosteoporotic agent that includes 2 strontium ions and an organic moiety (ranelic acid). Sr+2 can partially substitute Ca+2 in hydroxyapatite, and thus be incorporated into bone. SR has been shown to effectively reduce the risk of vertebral and femoral bone fractures in women with osteoporosis. In vitro, strontium increases osteoblast-mediated bone formation, while decreasing osteoclastic bone resorption. We study the release kinetics of Strontium in Alg hydrogels (HG). The HG were prepared with 2% Alg (Sigma-Aldrich) and 0.05, 0.1, 0.25 and 0.5 uM of Sr+2, the times of gelation were 1, 12 and 24hs. The release profile of Sr+2 from the HG was determined by incubating samples 1.0mL of sterile water at 37∘C for different periods of time. At appropriate times, the supernatant was removed and replaced by fresh water. The time-dependent release of the Sr+2 was followed by monitoring the amount of Sr+2 present in the supernatant medium, using a flame spectrophotometer. The assay was performed in quadruplicate and results were expressed as the fractional release (𝑀𝑡/𝑀∞) versus time of release (𝑡). Besides, swelling of all HG in water was studied. Our results show that Sr+2 concentrations released to medium depend of time gelation and the initial amount of strontium in the HG. In order to analyze the kinetics of Sr+2 releases, we used Fick?s second law. These results suggested that the mechanism of Sr+2 releases occurs by an Anomalous (non-Fickian) transport. As for the swelling of HG, a large percentage of these in some cases the 10,000% in 24hs are observed. In conclusion, we have obtained a delivery system Sr+2 with high swelling capacity.