Researchers have developed an inflammation-targeting hydrogel that preferentially adhered to inflamed epithelial surfaces and delivered corticosteroid medication more slowly and with less systemic drug exposure in preclinical models, suggesting it may be a promising approach for treating inflammatory bowel disease.
“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,” Jeff Karp, PhD, from Brigham and Women’s Hospital and Harvard Stem Cell Institute, said in a press release. “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.”
The hydrogel material was developed using ascorbyl palmitate, an FDA-approved amphiphile that can self-assemble into a hydrogel in vitro. The material is negatively charged and thus adheres to positively charged sites of tissue damage. Enzymes found only at these sites then break up the gel and slowly release medication.
“The materials we selected form a gel, which has the capacity to carry drugs,” Sufeng Zhang, PhD, a postdoctoral fellow at the David H. Koch Institute for Integrative Cancer Research at MIT, said in the release. “We designed the gel to both target inflamed tissue or ulcers and release drug only at sites of inflammation.”
To provide proof of concept for the hydrogel as a drug delivery platform for IBD, the researchers performed several studies. First, they characterized the inflammation-targeting hydrogel in vitro. Then, to assess the efficacy and systemic drug absorption of drug delivery via hydrogel enema, they administered dexamethasone-loaded hydrogels or traditional dexamethasone via enema in IBD mouse models and observed more effective reduction of inflammation with less frequent dosing with the hydrogel compared with free drug. According to the press release, there was also five to ten times lower serum corticosteroid concentrations with the hydrogel enema.
In additional mouse models and a study of colonic tissue samples from patients with ulcerative colitis, the researchers found the hydrogel preferentially adhered to inflamed lesions.
“Maximizing treatment of first line topical therapies for IBD and simultaneously minimizing the potential for side effects from these drugs is an extremely appealing option to both patients and health care providers given the significant risks associated with escalation of therapy which often include drugs which depress the immune system,” Giovanni Traverso, MD, PhD, from the division of gastroenterology at Massachusetts General Hospital, said in the release.
The researchers plan to repeat these studies using other classes of drugs and perform other preclinical studies before moving on to human trials, according to the release.
“Our study provides a good example of how therapies can be improved by exploiting disease-specific features for optimal drug delivery,” Joerg Ermann, MD, a rheumatologist at Brigham and Women’s Hospital, said in the release. “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.” – by Adam Leitenberger
Disclosure: Some of the investigators report they hold a patent related to this technology. Please see the full study for a list of all other authors’ relevant financial disclosures.