Modulation of the volume phase transition temperature for multi-stimuli-responsive copolymer hydrogels

Thermo-responsive (TR) hydrogels of the LCST (low critical solution temperature) type swell noticeably below their volume phase transition temperature T_c and collapse above T_c. Biomedical applications of these gels (in particular, for controlled delivery of nuclear acids and genes) require fine tuning of the critical temperature. Modulation of T_c is conventionally performed by copolymerization of TR monomers with monomers whose hydrophilicity is higher or lower than that of the main monomers. The most pronounced changes in T_c are observed when TR monomers are copolymerized with anionic or cationic monomers. Introduction of polyelectrolyte monomers into the polymer network induces a strong dependence of its properties on pH and ionic strength of an aqueous solution. A constitutive model is developed to describe the effects of pH and molar fraction of salt in a solution on the critical temperature of TR polyelectrolyte hydrogels. Adjustable parameters are found by fitting equilibrium swelling diagrams on copolymer gels with strongly and weakly dissociating cationic functional groups. The ability of the model to predict T_c is confirmed by comparison of experimental data with results of simulation.