Marine animals inspired scientists from the Massachusetts Institute of Technology in the United States and Novo Nordisk to develop a drug capsule that releases the drug directly into the stomach wall or other organs of the digestive system, ensuring that the drug reaches the right place without being affected by the surrounding conditions. The results of the new innovation were published in Nature magazine on November 20.
This capsule could provide an alternative method of delivering drugs that would normally have to be injected, such as insulin and other large proteins, including antibodies. This needle-free strategy could also be used to deliver RNA, either as a vaccine or therapeutic molecule to treat diabetes, obesity and other metabolic disorders.
“One of the challenges we were trying to overcome,” says Giovanni Traverso, director of the Translational Engineering Laboratory and associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, an associate member of the Broad Institute, and one of the researchers involved in the study, according to Science Daily. “They need to develop a method by which large drug molecules – which would normally have to be injected – can be delivered orally.”
Cephalopod molluscs as a source of inspiration
Medicines consisting of large proteins or RNA usually cannot be taken orally, because they are easily broken down in the digestive system before they reach their destination. For several years, Traverso’s lab has been working on ways to deliver such drugs orally by coating them to protect them from degradation, then injecting them directly into the lining of the digestive tract.
Most of these capsules use a small needle or set of tiny needles to deliver the medications once the device reaches the digestive tract. In the new study, Traverso and his colleagues wanted to develop a way to deliver these molecules without using any type of needle, which could reduce the potential for tissue damage.
To achieve this, they took inspiration from cephalopod molluscs such as octopuses and squid. Slugs have a unique ability to move and jet ink. The slugs use increased pressure in their mantle to force water and ink through a siphon that can be adjusted to change the direction of movement and ink jet.
Researchers have come up with two ways to mimic this squirting process, using pressurized carbon dioxide or tightly coiled springs to generate the force needed to push liquid drugs out of the capsule. The gas or spring is held in a compressed state by a catalyst designed to dissolve when exposed to moisture or an acidic environment such as that of a stomach. When the stimulator dissolves, the gas or spring is allowed to expand, pushing the medication out of the capsule. Capsules made of metal and plastic can pass through the gastrointestinal tract and be excreted in the feces after releasing their drug payload.
The researchers calculated in a series of experiments that the pressure needed to expel the drug is strong enough for it to penetrate the submucosal tissue in the wall of the digestive tract and accumulate there. The researchers also designed the capsules so that they can target different parts of the digestive system.
One version of this capsule, one with a flat bottom and a high dome, could sit on the surface of the stomach lining, for example, and release the drug down into the tissue.
Say goodbye to needles
The researchers envision that the ingestible capsule could be used at home by patients who need to take insulin or other frequently injected medications. In addition to making medication administration easier, especially for patients who do not like needles, this approach also eliminates the need to devise safe methods for disposing of sharp needles.
On the other hand, the researchers created and tested a version of the capsule that can be attached to an endoscope, allowing doctors to use it in endoscopic procedures.
The researchers did not discover any tissue damage caused by the release of the drug, and they plan to develop more capsules, in the hope of testing them in humans.