By making use of enzymes found in the digestive tract, MIT engineers have devised a way to
apply a temporary synthetic coating to the lining of the small intestine.
This coating could be adapted to deliver drugs, aid in digestion, or prevent nutrients such
as glucose from being absorbed.
In a study conducted in pigs, the 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.
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 catalyzed by an enzyme found in the small intestine.
The MIT team began working on this project with the goal of trying to develop liquid
drug formulations that could offer an easier-to-swallow alternative to capsules, especially for children.
Their idea was to create a polymer coating for the intestinal lining, which would form
after being swallowed as a solution of monomers.
They took their inspiration from nature and began to experiment 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 — the same chemical that acts as a neurotransmitter
in the brain.
The researchers discovered that an enzyme called catalase could help assemble molecules
of dopamine into the PDA polymer.
Catalase is found throughout the digestive tract, with especially high levels in the
upper region of the small intestine.
In a study conducted in pigs, the researchers showed that if they deliver dopamine in a
liquid solution, along with a tiny amount of hydrogen peroxide (at levels recognized
to be safe), catalase in the small intestine breaks the hydrogen peroxide down into water
and oxygen.
That oxygen helps the dopamine molecules to join together into the PDA polymer.
Within a few minutes, a thin film of PDA forms, coating the lining of the small intestine.
Once the researchers developed the coating, they began experimenting with ways to modify
it for a variety of applications.
In this study, the researchers showed that the coating lasts for 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.
The researchers performed some preliminary safety studies in rats and found that the
dopamine solution had no harmful effects.
Their studies also suggested that most or all of the dopamine molecules become part
of the synthetic coating and do not make it into the tissue or the bloodstream, but the
team plans to do additional safety studies to explore any possible effects the dopamine
may have.