Revolutionary insulin pill could do away with insulin injection in type 1 diabetes

"We are really pleased with the latest results of the new oral delivery device our lab members have developed with our collaborators, and we look forward to hopefully seeing it help people with diabetes and others in the future," says Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute for Integrative Cancer Research.

Most drugs are absorbed through the small intestine, Traverso says, in part because of its extremely large surface area -- 250 square meters, or about the size of a tennis court. Also, Traverso noted that pain receptors are lacking in this part of the body, potentially enabling pain-free micro-injections in the small intestine for delivery of drugs like insulin.

To allow their capsule to reach the small intestine and perform these micro-injections, the researchers coated it with a polymer that can survive the acidic environment of the stomach, which has a pH of 1.5 to 3.5. When the capsule reaches the small intestine, the higher pH (around 6) triggers it to break open, and three folded arms inside the capsule spring open.

Each arm contains patches of 1-millimetre-long microneedles that can carry insulin or other drugs. When the arms unfold open, the force of their release allows the tiny microneedles to just penetrate the topmost layer of the small intestine tissue. After insertion, the needles dissolve and release the drug.

"We performed numerous safety tests on animal and human tissue to ensure that the penetration event allowed for drug delivery without causing a full-thickness perforation or any other serious adverse events," Abramson says.

To reduce the risk of blockage in the intestine, the researchers designed the arms so that they would break apart after the microneedle patches are applied.

In tests in pigs, the researchers showed that the 30-millimetre-long capsules could deliver doses of insulin effectively and generate an immediate blood-glucose-lowering response. They also showed that no blockages formed in the intestine and the arms were excreted safely after applying the microneedle patches.

"We designed the arms such that they maintained sufficient strength to deliver the insulin microneedles to the small intestine wall, while still dissolving within several hours to prevent obstruction of the gastrointestinal tract," Caffarel-Salvador says.

Although the researchers used insulin to demonstrate the new system, they believe it could also be used to deliver other protein drugs such as hormones, enzymes, or antibodies, as well as RNA-based drugs.

"We can deliver insulin, but we see applications for many other therapeutics and possibly vaccines," Traverso says. "We're working very closely with our collaborators to identify the next steps and applications where we can have the greatest impact."

Source:

A luminal unfolding microneedle injector for oral delivery of macromolecules

DOI: https://doi.org/10.1038/s41591-019-0598-9