The disease-targeting hydrogel system sticks to sites of inflammation and releases medicine over time.
Image credit: BWH
So concludes a team from Brigham and Women's Hospital (BWH) in Boston who, with colleagues from other research centers, report their findings in Science Translational Medicine.
Inflammatory bowel disease (IBD) affects over 1 million Americans and is on the rise around the world. IBD is an umbrella term for a group of chronic, debilitating inflammatory intestinal conditions, including Crohn's disease and ulcerative colitis.
However, such treatments are not only uncomfortable and impractical, they can lead to side effects where drugs are absorbed by healthy tissue.
In their study, the researchers describe how a hydrogel made in the lab offers a potentially better way to deliver drugs in IBD via enemas that target inflamed tissue.
The team showed how the hydrogel stuck to sites of inflammation and slowly released the drug dose it was carrying over time.
Corresponding author Jeff Karp, an associate professor who heads a lab that develops advanced biomaterials and devices for therapeutics, says:
"We realized that if we could develop a disease-targeted hydrogel system that rapidly attaches to ulcers and slowly release drugs at the site of inflammation, then we could create a better way to deliver medicine only where the drug is needed."
Hydrogel would mean once-a-week instead of daily enemas for IBD
The researchers suggest their findings will lead to a type of enema that IBD patients will only have to use once a week instead of every day. Also, it will have no systemic side effects and there would be no need to retain the enema as the gel quickly attaches to ulcers.
To make the self-assembling hydrogel, the team used ascorbyl plamitate (AP), a material that is already approved for use in the US. AP is negatively charged and anchors itself to positively charged sites of tissue damage.
Co-first author Dr. Sufeng Zhang, a chemical engineer who is researching self-assembled hydrogels at the Massachusetts Institute of Technology (MIT) in Cambridge, says:
"The materials we selected form a gel, which has the capacity to carry drugs. We designed the gel to both target inflamed tissue or ulcers and release drug only at sites of inflammation."
The hydrogel incorporates a corticosteroid drug routinely used to treat IBD. The gel only disassembles to release the drug when it encounters a certain enzyme that is present at inflamed sites.
Tests showed the hydrogel delivered drug to inflamed sites
The team tested the hydrogel in two ways. First, they used mice genetically engineered to have a form of ulcerative colitis and showed that drugs delivered via the hydrogel relieved inflammation more effectively than when administered via traditional enemas.
- Crohn's disease is a type of IBD that causes inflammation of the lining of the digestive tract
- The disease often spreads deep into affected tissue
- Symptoms include diarrhea, fever, fatigue, nausea, vomiting, abdominal pains and cramps, blood in the stool, reduced appetite, and unintended weight loss.
The researchers also showed that in the mice that received the hydrogel-based therapy, their bloodstreams had 5-10 times lower concentrations of the drugs compared to mice receiving the drugs via traditional enema, suggesting the hydrogel-based delivery results in less drugs reaching the rest of the body.
And secondly, in tissue samples from human patients with ulcerative colitis and in another mouse model of colitis, the hydrogel showed a preference for sticking to inflamed regions rather than healthy tissue.
The team now plans to replicate these tests with other drugs and also run more preclinical tests before starting trials in humans.
Co-first author Dr. Joerg Ermann, a rheumatologist at BWH, says their study is a good example of how drug delivery can be improved by focusing on disease-specific features, and concludes:
"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."
In February 2014, Medical News Today learned how a team at the University of Illinois at Chicago is developing an approach that uses nanoparticles to treat inflammation-causing immune cells. The nanoparticle system precisely targets malfunctioning immune cells without interfering with cells that are functioning correctly.