Break through the mucus barrier and take large protein drugs orally

One reason why it is so difficult to take large protein drugs by mouth is that these drugs cannot pass through the mucus barrier
of the digestive tract.
This means that insulin and most other "biological drugs" — drugs made up of proteins or nucleic acids — must be injected or administered in
hospitals.
A new type of drug capsule developed by MIT may one day replace these injections
.
This capsule has an auto-rotating lid that, when it reaches the small intestine, crosses the mucus barrier and allows the drug carried by the capsule to enter the cells
of the intestinal wall.

"By replacing mucus, we can maximize the dispersion of the drug in local areas and enhance the absorption of small and large molecules," said
Giovanni Traverso, Karl van Tassel Career Development Assistant Professor of Mechanical Engineering at MIT and gastroenterologist at Brigham Women's Hospital.

In a study published today in the journal Science Robotics, researchers showed that they could use this method to deliver insulin and vancomycin, an antibiotic peptide
that must currently be injected.

For several years, Traverso's lab has been developing strategies
for protein drugs such as oral insulin.
This is a daunting task because protein-based drugs tend to be broken down in the acidic environment of the digestive tract, and they also have difficulty penetrating the mucus barrier
of the digestive tract.
To overcome these obstacles, Srinivasan came up with the idea of creating a protective capsule that included a mechanism to drill tunnels out of the slime like a tunnel boring machine drills into soil and rock
.

"I think if we can go through the mucus, then we can deposit the drug directly on
the epithelial cells," she said.
The idea is that when you ingest this capsule, its outer layer dissolves in the digestive tract, exposing all these features, starting to churn the mucus and clearing it
.
”

The capsule "RoboCap" is about the size of a multivitamin, it is loaded with a drug load at one end and has a tunneling function
on its body and surface.
The capsule is coated with gelatin on the surface to adjust its dissolution
at a specific pH.

When the coating dissolves, the change in pH triggers a tiny motor inside the RoboCap capsule to start spinning
.
This movement helps the envelope to enter the mucus and replace the mucus
.
The capsules are also coated with small nails that can brush off mucus, similar to the action of
a toothbrush.

The rotational movement also helps to erode the compartment that carries the drug, which is gradually released into the digestive tract
.

Traverso said: "What RoboCap does is temporarily replace the initial mucus barrier and then enhance absorption
by maximizing the dispersion of the drug locally.
By combining all these elements, we can really maximize our ability to provide the optimal environment
for the absorption of drugs.
”

intensifier

In animal trials, researchers used this capsule to deliver insulin, or vancomycin, a large peptide antibiotic used to treat a variety of infections, including skin infections and infections affecting orthopedic implants
.
The researchers found that in the absence of a tunneling mechanism, such capsules can release 20 to 40 times more drugs than similar capsules
.

Once the drug is released from the capsule, the capsule itself passes through the digestive tract
on its own.
The researchers found no signs of inflammation or irritation of the digestive tract after the capsule passed, and they also observed that the mucus layer changed
within a few hours after being replaced by the capsule.

Another way some researchers use to enhance oral administration of drugs is to use additional drugs at the same time as they are administered, helping the drug pass through the intestinal tissue
.
However, these enhancers are usually only effective
for certain drugs.
Traverso said that because the MIT team's new method relies entirely on mechanical destruction of the mucus barrier, it could be applied to a wider range of drugs
.

"Some chemical enhancers prioritize specific drug molecules," he said
.
"The use of mechanical administration methods may enhance the absorption
of more drugs.
"

While the capsule used in this study releases its load in the small intestine, it can also target the stomach or colon by changing the pH of the gelatin coating dissolved
.
The researchers also plan to explore the possibility of providing other protein drugs, such as GLP1 agonists, which are sometimes used to treat type 2 diabetes
.
This capsule can also be used to deliver topical medications to treat ulcerative colitis and other inflammatory diseases, helping to treat inflammation by maximizing the local concentration of the drug in tissues
.