Cellulose Nanocrystal-Based Sulfatase-Responsive Hydrogel for Sustained Celecoxib Release in Ulcerative Colitis Therapy.

Conventional treatments for ulcerative colitis (UC) are often associated with systemic side effects and require frequent dosing due to nonspecific drug distribution. Herein, a hydrogel based on poly(diallyldimethylammonium chloride) (PDADMAC) and cellulose nanocrystals (CNCs) was designed for the oral delivery of celecoxib in the treatment of UC. The hydrogel network incorporated sulfate ester groups, enabling sulfatase enzymes sensitive in the colon. Physiochemical characterization confirmed successful formation of the hydrogel, effective sulfate functionalization, and efficient drug encapsulation. Swelling studies revealed that the hydrogel maintained structural stability under different pH conditions, while in vitro and in vivo experiments demonstrated that drug release was markedly enhanced in the presence of sulfatase. Furthermore, the hydrogel showed improved drug loading efficiency and sustained release behavior. In a dextran sulfate sodium-induced UC mouse model, the celecoxib-loaded PDADMAC-CNC hydrogel effectively alleviated colonic inflammation, preserved colon structure, and reduced pro-inflammatory cytokine levels more markedly than free drug administration. This finding highlights the potential of sulfatase-responsive PDADMAC-CNC hydrogels as a targeted, safe, and effective approach for treating inflammatory bowel diseases, such as UC.