The new pill described in the Nature Biotechnology study maintains the same shape, allowing the capsule to orient itself correctly once it arrives in the stomach. However, the researchers redesigned the capsule interior so that it could be used to deliver liquid drugs, in larger quantities — up to 4 milligrams.
Delivering drugs in liquid form can help them reach the bloodstream more rapidly, which is necessary for drugs like insulin and epinephrine, which is used to treat allergic responses.
The researchers designed their device to target the stomach, rather than later parts of the digestive tract, because the amount of time it takes for something to reach the stomach after being swallowed is fairly uniform from person to person, Traverso says. Also, the lining of the stomach is thick and muscular, making it possible to inject drugs while mitigating harmful side effects.
The new delivery capsule is filled with fluid and also contains an injection needle and a plunger that helps to push the fluid out of the capsule. Both the needle and plunger are held in place by a pellet made of solid sugar. When the capsule enters the stomach, the humid environment causes the pellet to dissolve, pushing the needle into the stomach lining, while the plunger pushes the liquid through the needle. When the capsule is empty, a second plunger pulls the needle back into the capsule so that it can be safely excreted through the digestive tract.
In tests in pigs, the researchers showed that they could deliver a monoclonal antibody called adalimumab (Humira) at levels similar to those achieved by injection. This drug is used to treat autoimmune disorders such as inflammatory bowel disease and rheumatoid arthritis. They also delivered a type of protein drug known as a GLP-1 receptor agonist, which is used to treat type 2 diabetes.
“Delivery of monoclonal antibodies orally is one of the biggest challenges we face in the field of drug delivery science,” Traverso says. “From an engineering perspective, the ability to deliver monoclonal antibodies at significant levels really transforms how we start to think about the management of these conditions.”
Additionally, the researchers gave the animals capsules over several days and found that the drugs were delivered consistently each time. They also found no signs of damage to the stomach lining following the injections, which penetrate about 4.5 millimeters into the tissue.
David Brayden, a professor of advanced drug delivery at University College Dublin, who was not involved in the research, described the new approach as “a very exciting advance for the potential oral delivery of macromolecules. That similar blood levels to those arising from injections of these types of drugs can be achieved by stomach administration to large animals is a technical landmark for the field.”
The MIT team is now working with Novo Nordisk to further develop the system.
“Although it is still early days, we believe this device has the potential to transform treatment regimens across a range of therapeutic areas,” Rahbek says. “The ongoing research and development of this approach mean that several drugs that can currently only be administered via parenteral injections (non-oral routes) might be administered orally in the future. Our aim is to get the device into clinical trials as soon as possible.”
Other authors of the paper include MIT’s David H. Koch Institute Professor Robert Langer, Brian Jensen Mette Poulsen, Brian Mouridsen, Mikkel Oliver Jespersen, Rikke Kaae Kirk, Jesper Windum, Frantisek Hubalek, Jorrit Water, Johannes Fels, Stefan Gunnarsson, Adam Bohr, Ellen Marie Straarup, Mikkel Wennemoes Hvitfeld Ley, Xiaoya Lu, Jacob Wainer, Joy Collins, Siddartha Tamang, Keiko Ishida, Alison Hayward, Peter Herskind, Stephen Buckley, and Niclas Roxhed.
The research was funded by Novo Nordisk, the National Institutes of Health, the National Science Foundation, MIT’s Department of Mechanical Engineering, Brigham and Women’s Hospital’s Division of Gastroenterology, and the Viking Olof Bjork scholarship trust.