An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease
| Autor: | Bonnie Cao, Marc D. Succi, Joerg Ermann, Laurie H. Glimcher, Jonathan N. Glickman, Joshua R. Korzenik, Allen Zhou, Robert Langer, Giovanni Traverso, Jeffrey M. Karp, Praveen Kumar Vemula, Sufeng Zhang, Matthew J. Hamilton |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Colon
Biopsy medicine.medical_treatment Pharmacology Inflammatory bowel disease Dexamethasone Hydrogel Polyethylene Glycol Dimethacrylate Drug Delivery Systems Intestinal mucosa In vivo Animals Humans Medicine Intestinal Mucosa Colitis Inflammation Mice Inbred BALB C business.industry Macrophages General Medicine Enema Inflammatory Bowel Diseases medicine.disease Ulcerative colitis digestive system diseases Treatment Outcome Drug delivery Immunology business Ex vivo |
| Zdroj: | Science Translational Medicine. 7 |
| ISSN: | 1946-6242 1946-6234 |
| DOI: | 10.1126/scitranslmed.aaa5657 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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