Development of a Novel Enema Smart Hydrogel for Ulcerative Colitis (UC) Treatment
In this study, a novel MC/HA-Me enema smart hydrogel was developed for treating UC and the control of adhesion time to the intestinal wall was achieved by adjusting the ratio of MC and HA-Me compounds.
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.