Researchers from MIT and Novo Nordisk have created an innovative capsule ingestible inspired by squid propeller mechanisms. This capsule is designed to release drugs directly into the stomach wall or other organs in the digestive tract, offering a needle-free alternative for medications that usually require injections, such as insulin and large protein-based drugs, including antibodies.
The capsule releases drugs into the stomach or any other organs of the digestive system, eliminating the need for needles. This is a great alternative to injections that are usually required, like insulin, large proteins, and antibodies. Traditional oral delivery methods for drugs composed of large proteins or RNA are ineffective because these molecules tend to degrade in the digestive system.
MIT has been focused on creating devices to safely deliver such drugs orally by encapsulating them for years. Previously, many of these capsules relied on small needles to inject drugs once inside the digestive tract. However, the new approach eliminates the use of needles, thus minimizing potential tissue damage.
By observing cephalopods, researchers learned how squids and octopuses fill their mantle cavities with water and expel it through a siphon to propel themselves. This jetting mechanism also allows them to shoot ink clouds as a defense strategy. Inspired by this, the researchers devised two methods to mimic this jet propulsion in their capsules: compressed carbon dioxide or tightly coiled springs.
A carbohydrate trigger keeps the gas or spring under pressure. Once dissolved, the trigger dissolves upon exposure to moisture or acids in the stomach, expanding the gas or spring and pushing a jet of liquid drugs out of the capsule.
In their experiments, the researchers calculated the necessary pressures to expel drugs forcefully enough to penetrate the submucosal tissue, forming a depot that gradually releases the medication. They created two versions of the capsule tailored to target different sections of the digestive system. One version, shaped like a blueberry, features a flat bottom and a high dome, allowing it to rest on the stomach lining and eject drugs downward into the tissue.
| Version | Shape | Capacity | Target Area |
|---|---|---|---|
| 1 | Blueberry-shaped with flat base and high dome | 80 microliters | Stomach lining |
| 2 | Tube-like | 200 microliters | Sidewall of esophagus or small intestine |
Both capsule types are constructed from metal and plastic, enabling easy passage through the digestive system, where they are excreted after delivering their drug payload. In animal tests, these capsules successfully delivered insulin, a GLP-1 receptor agonist similar to Ozempic, and short interfering RNA (siRNA), a type of RNA capable of silencing specific genes, making it useful for treating various genetic disorders. The concentration of drugs in the animals' bloodstream reached levels comparable to those from direct injections, and no tissue damage was observed.
The researchers envision these ingestible capsules as a practical solution for patients requiring frequent insulin or other injected treatments. This approach not only simplifies drug administration for patients averse to needles but also eliminates the need for disposing of sharp objects. Additionally, they developed a variant attached to an endoscope that can deliver drugs in clinical settings like endoscopy suites or operating rooms.
The team plans to continue advancing the capsules and conduct human trials in the future. This groundwork lays a promising foundation for transforming how medications can be delivered, potentially improving the quality of life for many patients.