Designing Poly(Ethylene Glycol) Diacrylate Hydrogels with Controlled pH-Responsive Swelling

Polymer hydrogels are viscoelastic materials consisting of a flexible, crosslinked network that is highly swollen with water. In particular, “smart” hydrogels, in which the swelling of the polymer matrix changes with differences in environmental stimuli (temperature, pH, light exposure, salt concentration, etc.) are highly desirable for potential applications in fields such as drug delivery, microfluidics, tissue engineering and catalysis. In this work, we seek to engineer pH-responsive hydrogel nanoparticles as potential drug nanocarriers to trigger release upon cellular internalization. Poly(ethylene glycol) diacrylate (PEGDA) is used as an inexpensive, easily crosslinked, biocompatible hydrogelator that can be modified with pH-responsive co-monomers. Specifically, we study the incorporation of two ionizable co-monomers, 2-(dimethylamino)ethyl methacrylate (DMA) and 2-carboxyethyl acrylate (CEA) into PEGDA hydrogels, and characterize their effect on the pH-dependent equilibrium swelling of bulk hydrogels. Our results show that incorporation of the basic co-monomer DMA increases swelling at low pH levels and reduces swelling at high pH levels, whereas the opposite trend is observed for gels copolymerized with CEA, in agreement with expectations. These effects are exaggerated with increasing co-monomer content in the hydrogel. However, we find this differential swelling to be dependent on the PEGDA macromer concentration. Specifically, gels made from 0.7 kg/mol PEGDA exhibit significantly greater degrees of pH-differential swelling compared to those made from 6 and 10 kg/mol PEGDA. We hypothesize that this behavior is due to reduced incorporation of co-monomer into hydrogels of higher PEG chain length. Further experiments are aimed at translating this pH-responsive swelling to PEGDA co-polymer nanogels produced by nanoemulsion polymerization, in order to realize the potential of these materials to be used as drug nanodelivery vehicles with triggered release properties.