MIT Research Team Develops Micro-Injection Pill to Deliver Oral Insulin

Diabetes

The idea of swallowing a needle seems like a very bad idea. But a research team at Massachusetts Institute of Technology (MIT) has developed a capsule about the size of a blueberry that holds a tiny needle that, after being swallowed, injects insulin into the stomach.

In research animals, the capsule delivered enough insulin to decrease blood sugar levels comparable to those created by injections in the skin. The team also showed it could be modified to deliver other types of drugs.

“We are really hopeful that this new type of capsule could someday help diabetic patients and perhaps anyone who requires therapies that can now only be given by injection or infusion,” stated Robert Langer, the David H. Koch Institute Professor, one of the study’s senior authors.

The other senior author is Giovanni Traverso, a visiting scientist at MIT’s Department of Mechanical Engineering. Traverso is an assistant professor at Brigham and Women's Hospital, Harvard Medical SchoolLead author of the paper, which was published in the journal Science, is MIT graduate student Alex Abramson. Researchers with Novo Nordisk also were part of the research.

The first patient to receive an insulin rejection was a 14-year-old boy in Toronto, Canada. He received that life-saving shot in 1922. And ever since, researchers have been attempting to find ways to deliver insulin orally without any success. This MIT invention may finally break that losing streak.

“This field is really at an exciting state,” Samir Mitragotri, a biomedical engineer at Harvard University, told Science. “I think it’s going to completely transform how patients take drugs.”

The problem has largely been that insulin, a biologic, doesn’t survive in the stomach. Science notes, “Biologics, which include seven of the 10 top-selling drugs by sales in the United States, are more likely to hit a target molecule in the body without side effects because of their large size. But they’re also more liable to degrade in the stomach or be blocked from entering the bloodstream by thick layers of mucus and tightly packed epithelial cells that line the stomach and gut.”

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Traverso stated that getting past those obstacles “is honestly one of the biggest challenges and holy grails in drug development.”

In the MIT product, the pill contains a single needle that can inject the drugs into the interior of the stomach. The tip of the needle is built of almost 100 percent compressed, freeze-dried insulin. The needle’s shaft is built from a biodegradable material that doesn’t enter the stomach wall. The needle is attached to a tiny compressed spring held in place by a disk of sugar, all within the capsule.

When swallowed, water in the stomach dissolves the sugar disk, releases the spring, injecting the needle into the stomach wall. The stomach wall does not have pain receptors, so it’s unlikely patients would feel the injection.

The research team also solved another inherent problem—getting the capsule and needle to orient itself appropriately so it comes in contact with the stomach lining. They based their approach on a self-orientation aspect of the leopard tortoise, found in Africa. The leopard tortoise shell has a high, steep dome, which helps it roll back to its feet if it finds itself on its back.

The group created computer models to design a variant of the shape for their capsule, which allows it to orient itself even in the stomach. Or as some people might remember advertising from the 1970s for Weebles, “Weebles wobble, but they don’t fall down.” That toy’s egg shape and weighted bottom-center always righted the toy.

Abramson stated, “What’s important is that we have the needle in contact with the tissue when it is injected. Also, if a person were to move around or the stomach was to growl, the device would not move from its preferred orientation.”

The researchers are able to control the rate that insulin dissolves when they prepare the capsule. In their study, it took about an hour for it to be fully released into the bloodstream.

The research in pigs has successfully delivered up to 5 milligrams of insulin, comparable to the amount a type 2 diabetic patients would need to inject. Once the insulin is released, the capsule passes harmlessly through the digestive system. The capsule is built from a biodegradable polymer and stainless-steel components.

Maria Jose Alonso, professor of biopharmaceutics and pharmaceutical technology at the University of Santiago de Compostela in Spain, who was not involved in the research, stated, “We are not talking about incremental improvements in insulin absorption, which is what most researchers in the field have done so far. This is by far the most realistic and impactful breakthrough technology disclosed until now for oral peptide delivery.”

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