(721f) Modelling and Controlling Degradation and Protein Release Profile from Degradable Polymer-Polymer Hydrogel Depot

Hydrogels are suitable candidates as protein encapsulation depot and subsequent release process due to their hydrophilic environment. Degradable hydrogels are attractive because they eliminate the need for removal by surgery at the end of application as well as accelerating the protein release. To optimize the hydrogel design, it is crucial to have a clear understanding of network properties changes during degradation which has a considerable effect on drug release. In this research we propose a comprehensive model to account for combined effect of bulk-degradation, swelling and mass loss on the protein release for chemically crosslinked polymer-polymer hydrogels. Instead of extending eroding probability of one chain to the whole network by multiplying it to precursors initial weight fractions like previous models, more stochastic microscopic approach -Monte Carlo simulation scheme- was applied to obtain the detaching rate of polymer chains from network based on pseudo first order kinetic for crosslinkage cleavage as well as changes in cross-linking density. Bray-Merrill equation is utilized to obtain degradation kinetic rate constant through fitting with experimental volumetric swelling profile. Another advantage of this approach is that the effect of swelling on hydrogel mass loss fraction, its concentration and then drug release is included by solving diffusion-convection equation for both free polymer chains and drug in deformed geometry in which diffusion coefficient of drug and free polymer chains are function of hydrogel concentration. Initial network parameters such as molecular weight, degree of modification with reacting groups, concentration of polymeric precursors and types of degradable linker are expected to affect the erosion behavior of the network and drug release. Simulating the effect of these parameters on the degradation behavior would facilitate the design of degradable hydrogel systems for controlled release applications.