化学
炎症性肠病
活性氧
抗氧化剂
甲基丙烯酸酯
结肠炎
聚合
胃肠道
药理学
生物化学
高分子化学
免疫学
有机化学
聚合物
医学
病理
疾病
作者
Lenka Poláková,Vladimír Raus,Lucie Cuchalová,Rafał Poręba,Martin Hrubý,Jan Kučka,David Větvička,Olga Trhlíková,Zdeňka Sedláková
标识
DOI:10.1016/j.ijpharm.2021.121392
摘要
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.
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