Scientists create a synthetic lining for the intestine to make delivering drugs easier
Scientists have created a synthetic small intestinal lining designed to treat certain digestive diseases or make it easier for the body to absorb certain drugs — all contained in a solution that one day be could be gulped down in a single drink.
The small intestine is involved in a wide range of health conditions — from lactose intolerance to parasitic infections — and also plays a part in processing drugs. The new solution sticks to the lining of the small intestine and can be loaded up with drugs. The researchers found the solution was not only able to reach and coat the intestine, but also remained stable there for one day. The proof-of-concept research, conducted in pigs, rats, and human tissue, was published Wednesday in Science Translational Medicine.
“[This] now can be used for conducting … really interesting experiments, as well as a platform technology that can address several unmet needs. And it’s just a matter of time and resources to fully realize the potential of this technology,” said Jeffrey Karp, a biomedical engineer and professor at Harvard Medical School. Karp was not involved in the new research, but is affiliated with Brigham and Women’s Hospital in Boston, where several of the study’s authors also work.
The team — which also included scientists from Massachusetts Institute of Technology — first set out to create a new, simpler way for children to take their medications.
“We wanted to develop a liquid system that is easier to take compared to tablets or capsules, but had enhanced capabilities,” said Giovanni Traverso, a mechanical engineering professor at MIT and an author of the new study.
The result: a gastrointestinal synthetic epithelial lining system, or GSEL, which is a mixture of dopamine and minute amounts of hydrogen peroxide. This solution passes through the esophagus, stomach, and reaches the small intestine.
Certain cells in the small intestine have high amounts of catalase, an enzyme that breaks down hydrogen peroxide to release oxygen. These oxygen bubbles convert dopamine to a substance with strong adhesive properties, which helps the whole system stick to the small intestine.
In previous studies, researchers have developed tissue adhesives based on a similar concept to the one behind GSEL. But they’ve run into the challenges getting those materials to stick to the gastrointestinal tract, given that it’s so dynamic. The present research has overcome this challenge by “creating a micro-laboratory within the GI tract,” Karp said.
“Very few people would think about how you can make a polymer inside your body by your own enzyme or your own molecular chemical like dopamine,” said Junwei Li, the first author of the study.
The researchers tested the system in pig models to see whether it could have a therapeutic effect on lactose intolerance and abnormal glucose absorption. GSEL had a positive effect on both, which suggests it could be further studied as a treatment for type 2 diabetes, obesity, or lactose intolerance.
The researchers also looked at how GSEL could be used to deliver drugs. They tested the system with praziquantel, a drug used to treat schistosomiasis, a condition caused by a parasitic flatworm. The drug is taken three times a day. But the researchers found the GSEL layer extended the drug’s half-life significantly, meaning the drug was absorbed slowly into the body and might not need to be taken as often.
The researchers also tested the layer on human small intestine tissues and found similar results to those seen in pigs.
“It was reassuring to know that there were no significant adverse effects,” Traverso said.
But there’s still a need for more research on safety before moving testing into human trials. “We want to evaluate the potential effects of this formulation so that when it goes into a large population of human trials, it works uniformly and robustly,” Li said.