An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease

Sufeng Zhang; Joerg Ermann; Marc D. Succi; Allen Zhou; Matthew J. Hamilton; Bonnie Cao; Joshua R. Korzenik; Jonathan N. Glickman; Praveen K. Vemula; Laurie H. Glimcher; Giovanni Traverso; Robert Langer; Jeffrey M. Karp

doi:10.1126/scitranslmed.aaa5657

Research ArticleDrug Delivery

An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease

Sufeng Zhang¹,²,³,*,
Joerg Ermann⁴,⁵,*,
Marc D. Succi¹,²,⁵,
Allen Zhou²,
Matthew J. Hamilton⁵,⁶,
Bonnie Cao⁶,
Joshua R. Korzenik⁵,⁶,
Jonathan N. Glickman⁵,⁷,
Praveen K. Vemula⁸,
Laurie H. Glimcher⁹,
Giovanni Traverso¹,⁵,¹⁰,†,
Robert Langer¹,³,¹¹,† and
Jeffrey M. Karp²,⁵,¹¹,¹²,†

¹The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
²Center for Regenerative Therapeutics, Biomedical Research Institute, Brigham and Women’s Hospital, Boston, MA 02115, USA.
³Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁴Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, MA 02115, USA.
⁵Harvard Medical School, Boston, MA 02115, USA.
⁶Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA 02115, USA.
⁷Miraca Life Sciences, Newton, MA 02464, USA.
⁸Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore 560065, India.
⁹Weill Cornell Medical College, New York, NY 10065, USA.
¹⁰Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA.
¹¹Harvard–Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, MA 02139, USA.
¹²Harvard Stem Cell Institute, Cambridge, MA 02138, USA.

↵†Corresponding author. E-mail: rlanger{at}mit.edu (R.L.); jmkarp{at}partners.org (J.M.K.); ctraverso{at}partners.org (G.T.)

↵* These authors contributed equally to this work.

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Science Translational Medicine 12 Aug 2015:
Vol. 7, Issue 300, pp. 300ra128
DOI: 10.1126/scitranslmed.aaa5657

Sufeng Zhang

The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.Center for Regenerative Therapeutics, Biomedical Research Institute, Brigham and Women’s Hospital, Boston, MA 02115, USA.Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

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Joerg Ermann

Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, MA 02115, USA.Harvard Medical School, Boston, MA 02115, USA.

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Marc D. Succi

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Allen Zhou

Center for Regenerative Therapeutics, Biomedical Research Institute, Brigham and Women’s Hospital, Boston, MA 02115, USA.

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Matthew J. Hamilton

Harvard Medical School, Boston, MA 02115, USA.Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA 02115, USA.

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Bonnie Cao

Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA 02115, USA.

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Joshua R. Korzenik

Harvard Medical School, Boston, MA 02115, USA.Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA 02115, USA.

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Jonathan N. Glickman

Harvard Medical School, Boston, MA 02115, USA.Miraca Life Sciences, Newton, MA 02464, USA.

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Praveen K. Vemula

Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore 560065, India.

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Laurie H. Glimcher

Weill Cornell Medical College, New York, NY 10065, USA.

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Giovanni Traverso

The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.Harvard Medical School, Boston, MA 02115, USA.Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA.

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For correspondence: rlanger@mit.edujmkarp@partners.orgctraverso@partners.org

Robert Langer

The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.Harvard–Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, MA 02139, USA.

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For correspondence: rlanger@mit.edujmkarp@partners.orgctraverso@partners.org

Jeffrey M. Karp

Center for Regenerative Therapeutics, Biomedical Research Institute, Brigham and Women’s Hospital, Boston, MA 02115, USA.Harvard Medical School, Boston, MA 02115, USA.Harvard–Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, MA 02139, USA.Harvard Stem Cell Institute, Cambridge, MA 02138, USA.

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For correspondence: rlanger@mit.edujmkarp@partners.orgctraverso@partners.org

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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.

A hydrogel binds to inflamed tissues, delivering therapeutics locally and reducing systemic drug exposure in mouse models of inflammatory bowel disease.

An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease

Charged gels cozy up to inflamed tissues

Science Translational Medicine

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