Encapsulation of proteins in hydrogel carrier systems for controlled drug delivery: Influence of network structure and drug size on release rate

[Display omitted] ► Determination of hydrogel pore sizes by cryo-SEM and mesh sizes by swelling data. ► Pores and meshes assumed to be both present in the hydrogel system. ► Release influenced by the ratio of hydrodynamic diameter and mesh and pore size structure. ► Release of entrapped substances predominantly controlled by degradation. ► Release of appropriate dextrans as models is in line with the release of IgG and scFv. Novel hydrogels based on hydroxyethyl starch modified with polyethylene glycol methacrylate (HES-P(EG)6MA) were developed as delivery system for the controlled release of proteins. Since the drug release behavior is supposed to be related to the pore structure of the hydrogel network the pore sizes were determined by cryo-SEM, which is a mild technique for imaging on a nanometer scale. The results showed a decreasing pore size and an increase in pore homogeneity with increasing polymer concentration. Furthermore, the mesh sizes of the hydrogels were calculated based on swelling data. Pore and mesh size were significantly different which indicates that both structures are present in the hydrogel. The resulting structural model was correlated with release data for bulk hydrogel cylinders loaded with FITC-dextran and hydrogel microspheres loaded with FITC-IgG and FITC-dextran of different molecular size. The initial release depended much on the relation between hydrodynamic diameter and pore size while the long term release of the incorporated substances was predominantly controlled by degradation of the network of the much smaller meshes.