SHARP hydrogel for the treatment of inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a relapsing and remitting inflammatory disease affecting millions of people worldwide. The active phase of IBD is characterized by excessive formation of reactive oxygen species (ROS) in the intestinal mucosa, which further accelerates the inflammatory process. A feasible strategy for the IBD treatment is thus breaking the oxidation-inflammation vicious circle by scavenging excessive ROS with the use of a suitable antioxidant. Herein, we have developed a novel hydrogel system for oral administration utilizing sterically hindered amine-based redox polymer (SHARP) incorporating covalently bound antioxidant SHA groups. SHARP was prepared via free-radical polymerization by covalent crosslinking of 2-hydroxyethyl methacrylate (HEMA), poly(ethylene oxide) methyl ether methacrylate (PEGMA) and a SHA-based monomer, N-(2,2,6,6-tetramethyl-piperidin-4-yl)-methacrylamide. The SHARP hydrogel was resistant to hydrolysis and swelled considerably (∼90% water content) under the simulated gastrointestinal tract (GIT) conditions, and exhibited concentration-dependent antioxidant properties in vitro against different ROS. Further, the SHARP hydrogel was found to be non-genotoxic, non-cytotoxic, non-irritating, and non-absorbable from the gastrointestinal tract. Most importantly, SHARP hydrogel exhibited a statistically significant, dose-dependent therapeutic effect in the mice model of dextran sodium sulfate (DSS)-induced acute colitis. Altogether, the obtained results suggest that the SHARP hydrogel strategy holds a great promise with respect to IBD treatment.

Keywords: Antioxidant; Dextran sodium sulfate-induced colitis; Hydrogel; Inflammatory bowel disease; Reactive oxygen species; Redox polymer; Sterically hindered amine.