A new study from scientists at MIT has demonstrated a way to deliver mRNA directly to the digestive tract using a capsule. The researchers indicate this oral delivery system could be a unique way to administer mRNA therapies directly to the stomach.
Because our digestive system is filled with harsh acids designed to break down complex foods, oral drugs often need protective coatings to get past the stomach. Some drugs, such as insulin, need to be injected as researchers have struggled to develop effective ways to administer them orally.
A few years ago, MIT researchers revealed a unique method of oral drug administration. The innovation was a small capsule coated with microneedles. Upon reaching the intestines the capsule injects its contents directly into the wall of the gut and then harmlessly passes through a person’s digestive system.
In 2019, the MIT team demonstrated the capsule effectively delivered insulin in animal tests. In pig experiments the researchers found the capsule could get the same volume of insulin into the animal's bloodstream as a standard subcutaneous injection.
Now, in light of the remarkable pace of mRNA research due to the COVID-19 pandemic, the researchers have shown this novel drug delivery system can effectively work with mRNA molecules.
“Nucleic acids, in particular RNA, can be extremely sensitive to degradation particularly in the digestive tract,” said co-senior author on the new study, Giovanni Traverso. “Overcoming this challenge opens up multiple approaches to therapy, including potential vaccination through the oral route.”
First, the researchers developed a new kind of nanoparticle to hold the mRNA. This novel nanoparticle is designed to more effectively get into cells and deliver the mRNA payload, meaning fewer nanoparticles are needed to produce therapeutic effects.
After freeze-drying the nanoparticle payloads and packaging them into the microneedle capsules the researchers tested them out in several animal models. The mRNA being delivered in the experiments coded for the production of innocuous reporter proteins, which can signal the tissue is taking up the mRNA blueprint and manufacturing the desired molecules.
The pig experiments successfully demonstrated that stomach cells took up the mRNA molecules and produced reporter proteins. Alex Abramson, co-lead author on the new study, says more work is needed to explore whether mRNA vaccines administered this way can lead to systemic immune responses but it is plausible to think it could work due to the volume of immune cells in the gastrointestinal tract.
“There are many immune cells in the gastrointestinal tract, and stimulating the immune system of the gastrointestinal tract is a known way of creating an immune response,” said Abramson.
Beyond delivering mRNA vaccines in a new way, this new research points to exciting new targeted treatments for gastrointestinal diseases. mRNA can be used to ask cells to produce any number of molecules that could be therapeutically useful and delivering those blueprints directly to intestinal cells promises new ways to treat everything from ulcers to inflammatory bowel disease.
“When you have systemic delivery through intravenous injection or subcutaneous injection, it’s not very easy to target the stomach,” said Abramson. “We see this as a potential way to treat different diseases that are present in the gastrointestinal tract.”
The new study was published in the journal Matter.
Source: MIT
