Modeling Concentration Profiles of Infliximab in Colon Wall to Ensure Efficacy of Drug-Eluting Biodegradable Stent in the Management of Crohn's Disease
Dennin, Sean; Li, Xing; Yang, Danrui
Crohn’s disease (CD) is a chronic inflammatory disorder of the bowel affecting more than 500,000 people in the US. Current delivery mechanisms for CD medications lack site and time specificity. Advances in biomaterials have led researchers to look into biodegradable drug-eluting stent as a potential vehicle to overcome the aforementioned shortcomings of current treatments. In order to determine if such a treatment is feasible, we present a model for drug diffusion from a biodegradable with COMSOL 4.3. This model tracks the diffusion of infliximab from the degradable stent into the colon wall with time, as well as the drug degradation in the colon wall. We first compared the diffusion profiles of models with and without stent degradation. We then obtained the average concentration levels in the colon wall and compared it to minimum therapeutic level in literature. We also determined the effect of stent composition on stent degradation velocities. Furthermore, we studied the effect of varying model input parameters on concentration profiles and output parameters. Finally, we validated our model using an analytical solution for drug delivery from a degradable polymer. Our results indicate that stent degradation decreases the average end concentration by 12% to 14%. The average end concentration obtained with the degrading model is 9.923e-7 mg/mm3, higher than the minimum therapeutic level, and convergence is reached after 5.3 days. Our model is applicable for a wide range of clinical situations, drug compound choices and polymer choices.