Researchers have developed a swallowable capsule that twists and turns to break through the mucus barrier in the gastrointestinal tract, then releases its drug load. The "RoboCap" could thus make it possible to administer orally even "bulky" protein active ingredients that previously had to be injected. The researchers have already successfully demonstrated this potential using the example of insulin and a special antibiotic in pigs: The capsules enable the active ingredients to be absorbed in the small intestine and were excreted without any problems after their mission, the scientists report.
It is well known that many medications can be taken quite easily in the form of tablets, capsules and pills. These substances are easily absorbed by the body via the digestive system. However, this does not apply to a whole range of important active ingredients: in particular, drugs that consist of large proteins, such as insulin or certain antibiotics, cannot penetrate the mucous layers in the gastrointestinal tract. In this way, they do not advance to the mucous membrane cells that enable absorption into the body. Therefore, these substances have to be injected, which can be associated with problems.
How to overcome the slime barrier?
In order to make the sluggish substances orally administrable, the scientists led by Shriya Srinivasan from the Massachusetts Institute of Technology (MIT) in Cambridge are pursuing technical solutions. "I thought if we could dig a tunnel through the mucus, then we could deposit drugs directly onto the mucosal cells for improved uptake," says Srinivasan. "This gave rise to the idea of developing a capsule that can be swallowed and then break through layers of mucus," says the researcher.
This has finally led to the development of the RoboCap capsule. About the size of a typical multivitamin, it carries its drug payload in a small reservoir. The researchers equipped them with a tiny motor that rotates part of the capsule after activation in the gastrointestinal tract. In addition, the surface of the rotating element is provided with nubs, which can ensure a particularly effective whirling up of layers of mucus during the movement.
"The RoboCap temporarily dislodges the original mucus barrier and then enhances drug absorption by maximizing local drug release," says senior author Giovanni Traverso of MIT. The mechanism is triggered, followed by the drug being released after the gelatine coating of the capsule has dissolved. Due to adjustable characteristics of this substance, this dissolving process only occurs at certain pH values, as they exist in certain areas of the intestine, the scientists explain.
Successful tests
That's the theory. To what extent the system can actually do what it promises, the researchers tested on pigs as model animals for humans. You use the capsule to administer either the hormone insulin or vancomycin. This is a large peptide antibiotic that can effectively fight a wide range of bacterial infections. Both substances can normally only be absorbed by the intestine in very small amounts.
However, by administering it using the RoboCap capsule, the scientists achieved a 20 to 40 times higher transmission than with a similar capsule without the technical mechanism. The animal experiments also showed that the capsule passes through the digestive tract and is excreted without any problems after the drug has been released. The researchers also found no signs of inflammation or irritation in the digestive tract. As they explain, the affected mucus layer recedes soon after the disorder.
While the system still needs further testing, the scientists say it has significant potential: "By using this mechanical delivery method, some drugs could potentially be better absorbed," says Traverso. While the capsule used in this study releases its payload in the small intestine, it could also be used for the stomach or colon by altering the pH at which the gelatin coating dissolves, the researchers say. They now want to explore which drugs are particularly suitable for use with RoboCap in further experiments.
Source: Massachusetts Institute of Technology, professional article: Science Robotics, doi: 10.1126/scirobotics.abp9066