Film in the intestine
Using enzymes found in the digestive tract, engineers at the Massachusetts Institute of Technology have developed a way to apply a temporary synthetic coating to the mucous membrane of the small intestine. The technique can be adapted to deliver medications, promote digestion, or prevent the absorption of glucose and other nutrients.
Fragments of the small intestine of pigs – ordinary (left) and polymer-coated (right). Source: Junwei Li.
In a study conducted on pigs, researchers have demonstrated that gastrointestinal synthetic epithelial lining (GSEL) can be used to simplify the delivery of medications that usually need to be taken several times a day. They also modified GSEL to deliver lactase, an enzyme that helps people digest milk sugar lactose and block glucose absorption, which may offer a new tactic for treating diabetes or obesity.
GSEL is a polymer of dopamine molecules that can be consumed as a liquid. As soon as the solution reaches the small intestine, the molecules are assembled into a polymer in a reaction catalyzed by one of the enzymes of the small intestine.
Sticky polymers
The group started working on a project to develop liquid dosage forms that could become a more convenient alternative to capsules and tablets, especially for children. Their idea was to create a polymer coating for the intestinal mucosa, which would be formed after ingestion in the form of a solution of monomers – the building blocks of polymers.
Inspired by an example from nature, they began experimenting with a polymer called polydophamine (PDA), which is a component of the sticky substance secreted by mussels that helps them cling to stones. PDA consists of dopamine monomers.
The researchers found that the enzyme catalase helps dopamine molecules assemble into a PDA polymer. Catalase is common throughout the digestive tract, especially in the upper small intestine.
In an experiment on pigs, the researchers showed that a solution of dopamine with a small amount of hydrogen peroxide in the small intestine reacts with catalase, which breaks down hydrogen peroxide into water and oxygen. This oxygen helps dopamine molecules combine into the PDA polymer. Within a few minutes, a thin film of PDA is formed, covering the mucous membrane of the small intestine.
PDA has mucoadhesive properties, that is, GSEL can be very firmly attached to the intestinal wall.
The researchers experimented with ways to modify GSEL for various applications. They attached the enzyme beta-galactosidase (lactase) to it, and showed that such a coating increased the efficiency of lactose digestion in pigs by about 20 times.
In another experiment, the researchers used the anthelmintic drug praziquantel. It is usually necessary to take it three times a day, but as part of GSEL, one dose is enough, after which the drug is gradually released in the small intestine. According to the researchers, this approach may also be useful in the treatment of antibiotics that need to be administered more than once a day.
Finally, the researchers have shown that they can embed tiny crosslinking agents into GSEL that make the coating impervious to glucose (and possibly other molecules). According to the researchers, this will help in the treatment of diabetes, obesity and other metabolic disorders.
Temporary coverage
Researchers have shown that GSEL lasts about 24 hours, after which it is removed along with the cells of the intestinal mucosa, which is constantly being updated. Pigs received the solution using endoscopy, but the authors propose to develop a drinking form for humans.
Several preliminary studies on rats have shown that the dopamine solution does not have a harmful effect on the body. Safety is due to the fact that almost all dopamine molecules become part of the synthetic coating and do not penetrate into tissues or the bloodstream. However, the group plans to conduct additional safety studies to rule out any possible undesirable effects.
The researchers assessed the ability of the intestine to absorb nutrients 24 hours after taking the drug and found no differences between animals that were injected with GSEL and animals that did not receive it.
In addition, the group found that the polymer coating is able to attach well to the tissues of the human gastrointestinal tract.
Article J.Li el al. Gastrointestinal synthetic epithelial linings is published in the journal Science Translational Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to MIT News: Synthetic coating for the GI tract could deliver drugs or aid in digestion.