Abstract—Inflammatory Bowel Diseases (IBD), including Ulcerative Colitis (UC) and Crohn’s Disease (CD), are chronic autoimmune diseases with recurrent patterns that are not fully understood. In this study, a novel MC/HA-Me enema smart hydrogel was developed for treating UC. The HA-Me compound was synthesized through nucleophilic addition-elimination reactions at the acyl carbon (C = O) of Hyaluronic Acid (HA) with the amine groups (-NH2) of Mesalamine (Me). The structure of the HA-Me compound was identified using FTIR and H1-NMR spectroscopic techniques. The control of adhesion time to the intestinal wall was achieved by adjusting the ratio of MC and HA-Me compounds. An anti-inflammatory evaluation was conducted using Nitric Oxide (NO) assays with RAW 264.7 cells. The results indicated that the optimized formulation, consisting of 1 wt% NaCl, 6.5 wt% MC, and 4.5 wt% HA-Me, resulted in a gelling time of 238 seconds and a flow distance of 13.2 cm. This distance was closed to the length of the human rectum (about 12 cm~15 cm). The hydrogel containing Me drug can slowly release for up to 12 hours. Considering the results of cell survival rate, the optimal concentration of MC/HA-Me was 12.5 mM. In the future, we plan to increase the synthesis amount of HA-Me and conduct in vitro organoid simulation and animal experiments to evaluate the feasibility of enema smart hydrogels for human applications.  
 

Keywords—hyaluronic acid, mesalamine, methylcellulose, enema smart hydrogel, Inflammatory Bowel Diseases (IBD), Ulcerative Colitis (UC), anti-inflammatory