Self-assembling intestinal film blocks glucose uptake to treat diabetes
Maintaining healthy levels of glucose in the blood is a critical but often painstaking task for diabetics, involving regular insulin injections and fingerprick blood tests to ensure everything is kept in check. A new synthetic film developed at MIT could become a powerful tool in helping manage the disease, with the ability to self-assemble in the intestine to block the absorption of glucose and safely dissolve thereafter. And its potential mightn’t end there.
The film was developed by a group of MIT engineers who sought inspiration from the clingy capabilities of mussels, which are able to form rock-solid holds on objects thanks to a sticky substance they secrete. One key ingredient of this substance is polydopamine, a polymer made up of monomers of dopamine, which is the same neurotransmitter found in the human brain.
Digging into the details around how these polymers are formed, the team found that an enzyme called catalase plays an important role, enabling the individual molecules to assemble into the chain. Conveniently, catalase can also be found in our digestive tract, with high concentrations of it located in the upper part of the small intestine.
So the team got to work engineering a material that could be consumed as a liquid and used in place of drug capsules, by forming an intestinal lining to promote or reject uptake of drugs, nutrients and molecules.
“Children often aren’t able to take solid dosage forms like capsules and tablets,” says Giovanni Traverso, senior author of the study. “We started to think about whether we could develop liquid formulations that could form a synthetic epithelial lining that could then be used for drug delivery, making it easier for the patient to receive the medication.”
The researchers found that if dopamine is combined with a small amount of hydrogen peroxide in the liquid solution, the catalase in the small intestine produces oxygen and water in response. In turn, the oxygen causes the dopamine molecules to band together and form a PDA polymer film, which coats the small intestine in a matter of minutes.
“These polymers have muco-adhesion properties, which means that after polymerization, the polymer can attach to the intestinal wall very strongly,” says Junwei Li, lead author of the study. “In this way, we can generate synthetic, epithelial-like coatings on the original intestinal surface.”
This process was demonstrated in pigs, and once the team had established how the self-assembling film could be formed, they began to investigate the different ways it might be used. By embedding tiny crosslinkers into the polymer, they found they could make it impenetrable to glucose, a very promising capability that could one day offer an entirely new way for diabetics to manage their condition or help treat other metabolic disorders, such as obesity.
The researchers also experimented with other additives for the self-assembling polymer film. They found that by attaching the enzyme lactase, the film could improve the digestion of lactose around 20-fold. They also found that by integrating a medicine called praziquantel to treat the tropical disease schistosomiasis, the drug could be gradually released over the course of a day, a marked improvement on the three doses per day sufferers are currently required to take.
“These three applications are fairly distinct, but they offer a sense of the breadth of things that can be done with this approach,” says Traverso.
Importantly, the team also showed that the coating only lasts for around 24 hours before being disposed of by the natural processes that continually replace the intestinal lining. Testing on nutrient absorption after the film had been disposed of showed no difference between those animals that received it and a control group.
From here, the team will continue to investigate the safety of the technology, but note that some preliminary studies on rats are already showing some promising signs in this regard.
The research was published in the journal Science Translational Medicine, and the video below gives an overview of the research.