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Poláková L, Raus V, Cuchalová L, et al. SHARP hydrogel for the treatment of inflammatory bowel disease. Int J Pharm. 2021;613:121392doi: 10.1016/j.ijpharm.2021.121392.
Poláková, L., Raus, V., Cuchalová, L., Poręba, R., Hrubý, M., Kučka, J., Větvička, D., Trhlíková, O., & Sedláková, Z. (2021). SHARP hydrogel for the treatment of inflammatory bowel disease. International journal of pharmaceutics, 613121392. https://doi.org/10.1016/j.ijpharm.2021.121392
Poláková, Lenka, et al. "SHARP hydrogel for the treatment of inflammatory bowel disease." International journal of pharmaceutics vol. 613 (2021): 121392. doi: https://doi.org/10.1016/j.ijpharm.2021.121392
Poláková L, Raus V, Cuchalová L, Poręba R, Hrubý M, Kučka J, Větvička D, Trhlíková O, Sedláková Z. SHARP hydrogel for the treatment of inflammatory bowel disease. Int J Pharm. 2021 Dec 18;613:121392. doi: 10.1016/j.ijpharm.2021.121392. Epub 2021 Dec 18. PMID: 34933083.
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Int J Pharm. 2021 Dec 18;613:121392. doi: 10.1016/j.ijpharm.2021.121392. Epub 2021 Dec 18.

SHARP hydrogel for the treatment of inflammatory bowel disease.

International journal of pharmaceutics

Lenka Poláková, Vladimír Raus, Lucie Cuchalová, Rafał Poręba, Martin Hrubý, Jan Kučka, David Větvička, Olga Trhlíková, Zdeňka Sedláková

Affiliations

  1. Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského nám. 2, 162 06 Prague 6, Czech Republic. Electronic address: [email protected].
  2. Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského nám. 2, 162 06 Prague 6, Czech Republic.
  3. Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University, Salmovská 1, 120 00 Prague 2, Czech Republic.

PMID: 34933083 DOI: 10.1016/j.ijpharm.2021.121392

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.

Copyright © 2021 Elsevier B.V. All rights reserved.

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

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