An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease
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 repor...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Association for the Advancement of Science (AAAS)
2017
|
| Online Access: | http://hdl.handle.net/1721.1/109405 https://orcid.org/0000-0002-9481-2258 https://orcid.org/0000-0002-4260-2785 https://orcid.org/0000-0003-4255-0492 |
| _version_ | 1826208003125149696 |
|---|---|
| author | Ermann, J. Zhou, A. Hamilton, M. J. Cao, B. Korzenik, J. R. Glickman, J. N. Vemula, P. K. Glimcher, L. H. Zhang, Sufeng Succi, Marc David Traverso, Carlo Giovanni Langer, Robert S Karp, Jeffrey Michael |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Ermann, J. Zhou, A. Hamilton, M. J. Cao, B. Korzenik, J. R. Glickman, J. N. Vemula, P. K. Glimcher, L. H. Zhang, Sufeng Succi, Marc David Traverso, Carlo Giovanni Langer, Robert S Karp, Jeffrey Michael |
| author_sort | Ermann, J. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:58:47Z |
| format | Article |
| id | mit-1721.1/109405 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:58:47Z |
| publishDate | 2017 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1094052022-10-01T18:21:42Z An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease Ermann, J. Zhou, A. Hamilton, M. J. Cao, B. Korzenik, J. R. Glickman, J. N. Vemula, P. K. Glimcher, L. H. Zhang, Sufeng Succi, Marc David Traverso, Carlo Giovanni Langer, Robert S Karp, Jeffrey Michael Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Zhang, Sufeng Succi, Marc David Traverso, Carlo Giovanni Langer, Robert S Karp, Jeffrey 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. 2017-05-30T13:46:45Z 2017-05-30T13:46:45Z 2015-07 2014-12 Article http://purl.org/eprint/type/JournalArticle 1946-6234 1946-6242 http://hdl.handle.net/1721.1/109405 Zhang, S.; Ermann, J.; Succi, M. D.; Zhou, A.; Hamilton, M. J.; Cao, B.; Korzenik, J. R. et al. “An Inflammation-Targeting Hydrogel for Local Drug Delivery in Inflammatory Bowel Disease.” Science Translational Medicine 7, no. 300 (August 2015): 300ra128_1–300ra128_22 © 2015 American Association for the Advancement of Science (AAAS) https://orcid.org/0000-0002-9481-2258 https://orcid.org/0000-0002-4260-2785 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1126/scitranslmed.aaa5657 Science Translational Medicine Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Ermann, J. Zhou, A. Hamilton, M. J. Cao, B. Korzenik, J. R. Glickman, J. N. Vemula, P. K. Glimcher, L. H. Zhang, Sufeng Succi, Marc David Traverso, Carlo Giovanni Langer, Robert S Karp, Jeffrey Michael An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease |
| title | An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease |
| title_full | An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease |
| title_fullStr | An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease |
| title_full_unstemmed | An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease |
| title_short | An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease |
| title_sort | inflammation targeting hydrogel for local drug delivery in inflammatory bowel disease |
| url | http://hdl.handle.net/1721.1/109405 https://orcid.org/0000-0002-9481-2258 https://orcid.org/0000-0002-4260-2785 https://orcid.org/0000-0003-4255-0492 |
| work_keys_str_mv | AT ermannj aninflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT zhoua aninflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT hamiltonmj aninflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT caob aninflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT korzenikjr aninflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT glickmanjn aninflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT vemulapk aninflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT glimcherlh aninflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT zhangsufeng aninflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT succimarcdavid aninflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT traversocarlogiovanni aninflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT langerroberts aninflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT karpjeffreymichael aninflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT ermannj inflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT zhoua inflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT hamiltonmj inflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT caob inflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT korzenikjr inflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT glickmanjn inflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT vemulapk inflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT glimcherlh inflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT zhangsufeng inflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT succimarcdavid inflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT traversocarlogiovanni inflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT langerroberts inflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease AT karpjeffreymichael inflammationtargetinghydrogelforlocaldrugdeliveryininflammatoryboweldisease |