Novel GI tract coating could deliver drugs, aid digestion or control obesity

Engineers have designed a temporary synthetic coating that adheres to the lining on the small intestine and could be modified for drug delivery, aiding digestion or preventing specific nutrients from being absorbed, eg, glucose.

In a study conducted in pigs, MIT researchers demonstrated that they could use this approach to simplify the delivery of medications that normally have to be taken multiple times per day. They also modified the coatings to deliver the enzyme lactase, which helps people digest the milk sugar lactose, and to block glucose absorption, which could offer a new strategy to treat diabetes or obesity.

“These three applications are fairly distinct, but they offer a sense of the breadth of things that can be done with this approach,” said Dr Giovanni Traverso, an MIT assistant professor of mechanical engineering, a gastroenterologist at Brigham and Women’s Hospital and the senior author of the study.

The lining consists of a polymer made from dopamine molecules, which can be consumed as a liquid. Once the solution reaches the small intestine, the molecules are assembled into a polymer, in a reaction catalysed by catalase, an enzyme found in high concentrations in the upper region of the small intestine.

Exploring with polydopamine

The team initiated the project with the goal of developing liquid drug formulations that could offer an easier-to-swallow alternative to capsules. Their idea was to create a polymer coating for the intestinal lining, which would form after being swallowed as a solution of monomers. Traverso explained the work was particularly targeted at children who cannot take solid dosage forms.

They began experimentation with a polymer called polydopamine (PDA), which is a component of the sticky substance that mussels secrete to help them cling to rocks. PDA is made from monomers of dopamine, a neurotransmitter found in the brain.

The researchers discovered that the catalase enzyme found in the small intestine could help assemble monomers of dopamine into the PDA polymer.

In a study conducted in pigs, the researchers showed that if they deliver dopamine in a liquid solution, along with a small amount of hydrogen peroxide (at levels known to be safe), catalase in the small intestine breaks the hydrogen peroxide down into water and oxygen. The oxygen produced causes the dopamine molecules to form the PDA polymer. According to the team, within a few minutes a thin film of PDA forms, coating the lining of the small intestine.

“These polymers have muco-adhesion properties, which means that after polymerisation, the polymer can attach to the intestinal wall very strongly,” said Junwei Li, a postdoctoral researcher at MIT’s Koch Institute for Integrative Cancer Research and the lead author of the study. “In this way, we can generate synthetic, epithelial-like coatings on the original intestinal surface.”

Once the researchers developed the coating, they began experimenting with ways to modify it for a variety of applications. They showed that they could attach an enzyme called beta-galactosidase (lactase) to the film to help with lactose digestion. In pigs, this coating improved the efficiency of lactose digestion by around 20-fold.

Researchers also developed a formulation incorporating the drug praziquantel, which is used to treat schistosomiasis, a tropical disease caused by parasitic worms. Usually this drug has to be given three times a day, but using this formulation, it could be given just once a day and gradually released over 24 hours. The researchers said the test was a proof-of-concept that the approach could be useful for antibiotics that have to be given more than once a day.

Lastly, the researchers showed that they could embed the polymer with tiny crosslinkers that make the coating impenetrable to glucose (and potentially other molecules). The crosslinker formulation could help in the management of diabetes, obesity or other metabolic disorders, said the team.

A temporary coating

The engineers reported that their coating lasts about 24 hours, after which it is shed along with the cells that make up the intestinal lining, which is continually replaced. For their studies in pigs, the researchers delivered the solution by endoscopy, but they envision developing a drinkable formulation for human use. The researchers are also developing other alternative formulations, including capsules and pills.

In preliminary safety studies performed in rats, the team said the dopamine solution had no harmful effects and that most or all of the dopamine molecules become part of the synthetic coating and did not enter tissue or the bloodstream. They plan to do additional safety studies to explore any possible effects the dopamine solution may have.

Moreover, the researchers investigated the nutrient absorption capacity of the intestine after 24 hours and showed no difference between animals that had received the gastrointestinal synthetic epithelial lining (GSEL) and those that had not received it.

Additionally, the team found that the coating was able to stick well to human gastrointestinal tissue.

The study was published in Science Translational Medicine.