The Synthesis and Characterization of a Novel Polysaccharide Hydrogel for Biomedical Applications Including the Treatment of Malignant Tumors and the Prevention of Metastatic Disease

Abstract

Amygel® is an injectable biodegradable controlled release drug delivery system with adjustable release kinetics determined by varying the concentrations of the polymeric components of the material. Amygel® is a starch based biodegradable hydrogel consisting of an interpenetrating network of physically entangled amylose and amylopectin polymer chains crosslinked with d-glucaric acid. Amylose and amylopectin are the two components of naturally occurring starch. The immiscibility of the amylose and amylopectin due to differences in solubility parameter and chain size induces phase separation within the network but because the chains entangled during hydrolysis an interpenetrating network is formed. The chemically reactive carboxyl groups of the dglucaric acid react with the –OH groups of the amylose and amylopectin chains via condensation creating an ester linkage. This ester linkage degrades according to the same hydrolytic mechanism of the main chain backbone resulting in the release of di-acid while the hydrolysis of the acetal bonds of the amylose and the amylopectin results in the generation of glucose monomers, maltose dimers, and maltotriose trimers which can all be safely consumed by the surrounding cells in the tissue. Raman Spectroscopy confirms the formation of ester linkages with the addition of d-glucaric acid to starch gels. With the addition of the chemical crosslinker, the elastic modulus of the starch hydrogel increases. Also, with increased crosslink concentration, the degradation time of the system is extended. D-glucaric acid is a proven anti-carcinogenic agent, and there is evidence that Amygel® inhibits the cell proliferation of osteosarcomas by up to 70%