Researchers have developed a drug that can break through the mucus barrier
A capsule that tunnels through mucus in the gastrointestinal tract could be used to orally administer large protein drugs such as insulin.
A large protein drug capsule recently developed at the Massachusetts Institute of Technology (MIT), US, can pass through the mucus barrier that lines the digestive tract. Usually, these types of drugs are hard to deliver orally because it cannot pass through the mucus barrier that lines the digestive tract.
The capsule has a robotic cap that spins and tunnels through the mucus barrier when it reaches the small intestine, allowing drugs carried by the capsule to pass into cells lining the intestine. In their study, recently published in Science Robotics, the researchers demonstrated that they could use this approach to deliver insulin as well as vancomycin, an antibiotic peptide that currently must be injected.
The “RoboCap” capsule carries its drug payload in a small reservoir at one end and carries the tunnelling features in its main body and surface. The capsule is coated with gelatine that can be tuned to dissolve at a specific pH.
When the coating dissolves, the change in pH triggers a tiny motor inside the RoboCap capsule to start spinning. This motion helps the capsule to tunnel into the mucus and displace it. The capsule is also coated with small studs that brush mucus away. The spinning motion also helps to erode the compartment that carries the drug, which is gradually released into the digestive tract.
In tests in animals, the researchers used this capsule to deliver either insulin or vancomycin, a large peptide antibiotic that is used to treat a broad range of infections, including skin infections as well as infections affecting orthopaedic implants. With the capsule, the researchers found that they could deliver 20 to 40 times more drug than a similar capsule without the tunnelling mechanism.
Once the drug is released from the capsule, the capsule itself passes through the digestive tract on its own. The researchers found no sign of inflammation or irritation in the digestive tract after the capsule passed through, and they also observed that the mucus layer reforms within a few hours after being displaced by the capsule.
Another approach that some researchers have used to enhance oral delivery of drugs is to give them along with additional drugs that help them cross through the intestinal tissue. However, these enhancers often only work with certain drugs. The researchers say that as their new approach relies solely on mechanical disruptions to the mucus barrier, it could potentially be applied to a broader set of drugs.
While the capsule used in this study released its payload in the small intestine, it could also be used to target the stomach or colon by changing the pH at which the gelatine coating dissolves. The researchers also plan to explore the possibility of delivering other protein drugs such as GLP1 receptor agonist, which is sometimes used to treat type 2 diabetes. The capsules could also be used to deliver topical drugs to treat ulcerative colitis and other inflammatory conditions by maximising the local concentration of the drugs in the tissue to help treat the inflammation.