Modeling of small-molecule release from crosslinked hydrogel microspheres: effect of crosslinking and enzymatic degradation of hydrogel matrix

A diffusion-based model describing the drug release from a charged hydrogel (gelatin) microsphere undergoing enzymatic degradation is presented. The model elucidates the effect of glutaraldehyde, a crosslinking agent, on the release profile in terms of the initial drug distribution, diffusivity of the drug, degradation rate of gelatin and its ability to form polyionic complex with the drug. The model was validated by comparing with in vitro release of trypan blue, an acidic model drug, from basic gelatin microspheres. While drug release was not a simple function of glutaraldehyde concentration, the effective diffusivity was found to be inversely proportional to glutaraldehyde concentration in the form of a power function when the initial drug distribution was taken into consideration. For these reasons, the present model can accurately predict drug release with no adjustable parameters, given the collagenase concentration. The present model may help design certain release scenarios from biodegradable charged hydrogels for the oppositely charged drugs and biomolecules.