Slow-release hydrogel targets sites of inflammatory bowel disease

Researchers have developed a slow-release, inflammation-targeting hydrogel for patients with chronic inflammatory bowel disease (IBD), which could reduce uncomfortable, enema-based treatment from once-daily to once-weekly, according to a study published August 12, 2015 in Science Translational Medicine.

Investigators in and around Boston, MA—from Brigham and Women’s Hospital (BWH), Massachusetts General Hospital (MGH), and Massachusetts Institute of Technology (MIT)—sought to deliver anti-inflammatory treatment directly to the surface of the colon.

“We realized that if we could develop a disease-targeted hydrogel system that rapidly attaches to ulcers and slowly releases drugs at the site of inflammation, then we could create a better way to deliver medicine only where the drug is needed,” said co-corresponding author Jeff Karp, PhD, of the BWH Department of Medicine and a principal investigator at Harvard Stem Cell Institute, in Cambridge, MA. “We’re hopeful that this technology will allow patients to take an enema once a week rather than every day and without systemic side effects or the need to retain the enema as the gel quickly attaches to ulcers, ultimately improving their quality of life.”

For this study, the investigators developed hydrogel microfibers from ascorbyl palmitate, an FDA-approved compound that possesses both hydrophilic and lipophilic properties. This negatively-charged hydrogel can be disassembled by enzymes found only in inflamed tissue, which is positively charged. The investigators loaded the hydrogel with dexamethasone, which is commonly used to treat IBD. When the inflammation-targeting hydrogel drug meets such enzymes, the molecules that make up the gel begin to break apart, slowly releasing the dexamethasone.

To test the drug delivery system, the researchers administered it as an enema in mice genetically designed for ulcerative colitis. They found their hydrogel drug achieved a significant reduction in inflammation with less frequent dosing when compared to traditional corticosteroid-containing enemas. The team also found that treated mice had 5 to 10 times lower corticosteroid concentrations in the bloodstream, indicating less drug exposure throughout the body.

In addition to these in vivo mouse models, the team also tested the gel in colon tissue samples from human patients with IBD. They found that the hydrogel preferentially adhered to inflamed lesions rather than to normal tissue. The team plans to repeat their studies using other classes of drugs and test the gel in additional preclinical models before administering it in human patients.

“Our study provides a good example of how therapies can be improved by exploiting disease-specific features for optimal drug delivery,” said Joerg Ermann, MD, a rheumatologist at BWH and co-first author. “We have found that the hydrogel approach works well in mice and our data look promising that it might also be an effective strategy in humans with inflammatory bowel disease of the colon.”