Protein medications, a drug delivery capsule could be used instead of injections.

Monoclonal antibodies — proteins that replicate the body's own immune defenses — have recently been discovered by scientists to fight a number of ailments, including certain malignancies and autoimmune disorders like Crohn's disease. While these medications are effective, one disadvantage is that they must be injected.

In conjunction with scientists from Brigham and Women's Hospital and Novo Nordisk, a group of MIT engineers is developing an alternate delivery approach that could make it much easier for patients to benefit from monoclonal antibodies and other injectable medications. Patients would simply take a capsule containing the medicine, which would subsequently be injected straight into the stomach lining.

"If we can make it easier for patients to take their medication, it will be more likely that they will take it, and healthcare providers will be more likely to adopt therapies that are known to be effective," says Giovanni Traverso, a gastroenterologist at Brigham and Women's Hospital and the Karl van Tassel Career Development Assistant Professor of Mechanical Engineering at MIT.

The researchers proved that their capsules may be used to deliver not only monoclonal antibodies but also other big protein medications like insulin to pigs in a study published today in Nature Biotechnology.

The paper's principal authors are Traverso and Ulrik Rahbek, vice president of Novo Nordisk. The principal authors are former MIT graduate student Alex Abramson and Novo Nordisk scientists Morten Revsgaard Frederiksen and Andreas Vegge.

The stomach is the target.

Because enzymes in the digestive tract break down large protein medications before they can be absorbed, most large protein pharmaceuticals can't be taken orally. Traverso and his colleagues have been working on a variety of ways for delivering such medications orally, and in 2019, they developed a capsule that can inject up to 300 micrograms of insulin.

The leopard tortoise inspired the high, steep dome on that pill, which is about the size of a blueberry. The capsule can orient itself so that its needle may be inserted into the stomach lining, similar to how a tortoise can right itself if it rolls onto its back. The needle tip in the original form was compressed insulin, which dissolved in the tissue after being delivered into the stomach wall.

The novel pill revealed in the Nature Biotechnology paper keeps its shape, allowing the capsule to properly orient itself once it reaches the stomach. The researchers, on the other hand, altered the capsule's interior to allow it to deliver liquid medications in bigger doses — up to 4 milligrams.

Medications delivered in liquid form can reach the bloodstream faster, which is important for drugs like insulin and epinephrine, which is used to treat allergic reactions.

Because the length of time it takes for something to reach the stomach after being eaten is fairly similar from person to person, the researchers developed their gadget to target the stomach rather than later portions of the digestive tract. In addition, the stomach lining is strong and muscular, allowing for the injection of medications while minimizing negative side effects.

The new delivery capsule is loaded with fluid and has an injection needle as well as a plunger to help force the fluid out. A solid sugar pellet holds both the needle and the plunger in place. When the capsule enters the stomach, the pellet dissolves in the humid environment, forcing the needle into the stomach lining while the plunger forces the liquid through the needle. A second plunger draws the needle back into the capsule when the capsule is empty, allowing it to be safely eliminated through the digestive tract.

Significant Level

The researchers demonstrated in pigs that they could deliver a monoclonal antibody called adalimumab (Humira) at levels comparable to injection. This medication is used to treat autoimmune diseases such rheumatoid arthritis and inflammatory bowel disease. They also supplied a GLP-1 receptor agonist, which is a type of protein medication used to treat type 2 diabetes.

"Oral administration of monoclonal antibodies is one of the most difficult difficulties we confront in drug delivery technology," adds Traverso. "The capacity to administer monoclonal antibodies at considerable amounts affects how we start to think about the management of these illnesses from an engineering standpoint."

Furthermore, the researchers administered capsules to the animals across multiple days and discovered that the medications were supplied reliably each time. Following the injections, which penetrate roughly 4.5 millimeters into the tissue, they detected no symptoms of harm to the stomach lining.

The MIT team is now collaborating with Novo Nordisk on furthering the system's development.

"Although it is still early days," Rahbek says, "we feel this device has the potential to change therapy regimens across a variety of therapeutic areas." "Because of the ongoing study and development of this strategy, some medications that are currently only available via parenteral injections (non-oral routes) may soon be available orally. The device will be put into clinical trials as soon as possible."