You are currently viewing the abstract.
View Full TextLog in to view the full text
AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have purchased individual subscriptions.
Register for free to read this article
As a service to the community, this article is available for free. Existing users log in.
More options
Download and print this article for your personal scholarly, research, and educational use.
Buy a single issue of Science for just $15 USD.
Charged gels cozy up to inflamed tissues
Inflammation is a driving factor of many chronic diseases, such as inflammatory bowel disease (IBD). To get potent drugs right to the site of inflammation, Zhang et al. designed a negatively charged hydrogel that could self-assemble and deliver hydrophobic anti-inflammatory drugs directly to the inflamed colon surface, which is positively charged. Dexamethasone-loaded hydrogels were administered as an enema to a genetic mouse model of ulcerative colitis (UC)—a type of IBD. The hydrogels relieved inflammation in the animals more effectively than did the free drug, which runs the risk of also affecting healthy tissues. In tissue samples from patients with UC and in another chemically induced mouse model of colitis, the hydrogel microfibers preferentially stuck to the inflamed regions. These findings together suggest that this new gel-based delivery system could reach and directly treat areas of epithelial inflammation in humans.
Abstract
There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. Targeting drugs selectively to the inflamed intestine may improve therapeutic outcomes and minimize systemic toxicity. We report the development of an inflammation-targeting hydrogel (IT-hydrogel) that acts as a drug delivery system to the inflamed colon. Hydrogel microfibers were generated from ascorbyl palmitate, an amphiphile that is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration. IT-hydrogel microfibers loaded with the anti-inflammatory corticosteroid dexamethasone (Dex) were stable, released drug only upon enzymatic digestion, and demonstrated preferential adhesion to inflamed epithelial surfaces in vitro and in two mouse colitis models in vivo. Dex-loaded IT-hydrogel enemas, but not free Dex enemas, administered every other day to mice with colitis resulted in a significant reduction in inflammation and were associated with lower Dex peak serum concentrations and, thus, less systemic drug exposure. Ex vivo analysis of colon tissue samples from patients with ulcerative colitis demonstrated that IT-hydrogel microfibers adhered preferentially to mucosa from inflamed lesions compared with histologically normal sites. The IT-hydrogel drug delivery platform represents a promising approach for targeted enema-based therapies in patients with colonic IBD.
- Copyright © 2015, American Association for the Advancement of Science
