Modelling the conformational change dynamics of pHsensitive cationic hydrogels : a case of genipin crosslinked chitosan hydrogels

Abstract

pH responsive hydrogels are increasingly gaining grounds in medical and pharmaceutical fields, because of their ability to respond to pH variations in the body or disease site. Design and optimization of these systems for controlled drug delivery, tissue engineering and other applications require insight into the dynamics of volume variation of these materials. The conformational change dynamics of these materials when they are in contact with environments with different pH depends on the nature of the functional group attached to the backbone of the hydrogel. For hydrogels with negative fixed charged group at the backbone (that is, anionic hydrogels) their response to pH variation in the surrounding medium has been previously reported and was used to initially validate the developed anionic model before moving on to chitosan-based hydrogels. However, for cationic hydrogels (those having positive fixed charge group at their backbone) most studies have been empirical due to the complexity associated with numerical modelling of their reversible swelling-shrinking dynamics. The deformation of hydrogel in aqueous environment is a multiphysics problem that involves the interactions of chemical, electrical and mechanical fields. To describe the conformational change dynamics of the hydrogel, the numerical model should capture adequately these interacting fields. Therefore, in this study numerical modelling of the dynamic volume variation behaviour of cationic hydrogels; particularly genipin crosslinked chitosan hydrogel was approached systematically. A multifield numerical model was first developed using COMSOL Multiphysics software to simulate the equilibrium swelling behaviour of anionic hydrogels. The performance capacity of the model was evaluated using experimental data for poly (2-hydroxyethyl methacrylate), PHEMA hydrogel. Further, the simulation platform developed for anionic hydrogels was adapted to cationic hydrogels. However, obtaining a dynamic simulation was difficult owing to numerical issues such as stability and stiffness. Although steady-state solutions were obtained, each time the pH of the surrounding medium changed from acidic to alkaline, it was required to manually change the boundary conditions especially during shrinking of the hydrogel. To circumvent this challenge, a systematic approach that combines thermodynamics modelling with chemo-mechanical modelling was adopted. The simulation results agreed with experimental data during validation. Thus, it is concluded that the model can predict the time evolution of the volume of cationic hydrogels.