Synthesis of thermally and pH-responsive poly(2-(dimethylamino)ethyl methacrylate)-based hydrogel reinforced with cellulose nanocrystals for sustained drug release.

Hydrogels are widely employed in biomedical applications due to their high swelling potential, tailored mechanical properties, biocompatibility, and ability to incorporate drugs to modify their release behavior. This study explored the synthesis of dual stimuli-responsive composite hydrogels by combining poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) with 4, 8, and 12 % (w/w) of cellulose nanocrystals (CNC) through in-situ free-radical polymerization, modifying their properties for topical anti-inflammatory release. Although PDMAEMA-based hydrogels have been known for their responsiveness to pH and temperature stimuli, which are useful for modulating the release profile of drugs, their use as a matrix for anti-inflammatory topical applications remains unexplored. Thus, a comprehensive analysis of CNC concentration's impact on PDMAEMA-based hydrogel structure and physicochemical properties is provided. The incorporation of ibuprofen as an anti-inflammatory model was assessed, providing insights into the potential of these composite hydrogels for sustained drug delivery applications. Overall, the hydrogels exhibited homogenous CNC dispersion, with gel fraction higher than 70 % and ibuprofen load higher than 90 %. The rise in CNC concentration led to an increase hydrogel stiffness. Finally, the CNC incorporation also modified the ibuprofen release to a more sustained profile, following the Peppas-Sahlin model, which may be attractive for developing pharmaceutical devices for different therapeutical scenarios.