Dextran hydrogels for the controlled release of proteins

Abstract

The release of proteins from non-degrading and enzymatically degrading dextran hydrogels was investigated. These dextran hydrogels were obtained by radical polymerization of aqueous solutions of glycidyl methacrylate derivatized dextran (dex-GMA). It was shown by FTIR analysis that by a proper selection of the polymerization conditions, hydrogels could be obtained in which more than 95% of the methacrylate groups had reacted within 20 min. The release of three model proteins (lysozyme, albumin, IgG) from non-degrading dextran gels with a varying initial water content and crosslink density was studied. For gels with a high equilibrium water content, the amount of protein released was proportional to the square root of time. The diffusion of proteins in these highly hydrated gels could be effectively described by the free volume theory. On the other hand, the release of the proteins from hydrogels with a low hydration level was marginal and did not follow the free volume theory, indicating that in these gels screening occurred. Dextran hydrogels can be made degradable by coencapsulation of dextranase. The degradation rate could be established by determination of reducing oligosaccharides and was dependent on the amount of dextranase in the gel. The release of a model protein (IgG) from degrading dextran hydrogels was investigated as a function of the amount of dextranase present in the gel and the gel characteristics. In the absence of dextranase no significant release of IgG from the hydrogels occurred, indicating that the protein diameter is larger than the hydrogel mesh size. However, in the presence of dextranase the release of IgG from the gels abruptly increased after a certain time when the enzyme had degraded the hydrogel to a certain extent.