Delayed release of a model protein from enzymatically-degrading dextran hydrogels

Enzymatically-degrading dextran hydrogels were investigated as matrices for the delayed release of proteins. The hydrogels were prepared by radical polymerization of aqueous solutions of glycidyl methacrylate-derivatized dextran (dex-GMA). Degradation was accomplished by incorporation of an endo-dextranase. The degradation rate of the gels was determined by measuring the release of reducing oligosaccharides, which are products of the degradation process. The release of a model protein (IgG) was studied as a function of several factors including the concentration of dextranase, the initial water content of the gel and the degree of GMA substitution determining the crosslink density of the gel. In the absence of dextranase, IgG was released very slowly for a period of 250 days. For gels containing dextranase, the release profile was highly dependent on the concentration of enzyme present in the gel. At a relatively high concentration of dextranase (1 U/g gel), the release of IgG started immediately and was completed within 5 to 10 days, while at lower concentrations (0.001-0.03 U/g,eel) a delayed release pattern was observed. A correlation was found between the length of the delay and the degradation rate of the hydrogel. Furthermore, this degradation rate was strongly affected by both the concentration of dextranase in the gel and the crosslink density of the gel. On the other hand, both the degradation rate and the release of IgG were independent of the initial water content of the hydrogel. The release of dextranase was substantially slower than expected, which was attributed to the binding of the enzyme to the dextran network in the hydrogel.