The advance by MIT engineers in collaboration with scientists from Novo Nordisk overcomes the limitations of protein-based drugs that would normally break down in the gastrointestinal tract if taken orally.
Instead, when the new the capsule reaches the small intestine, it breaks down to reveal dissolvable microneedles that attach to the intestinal wall and release drug for uptake into the bloodstream.
"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," said Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute for Integrative Cancer Research.
In tests in pigs, the researchers showed that this capsule could load a comparable amount of insulin to that of an injection, enabling fast uptake into the bloodstream after the microneedles were released.
Langer and Giovanni Traverso, an assistant professor in MIT's Department of Mechanical Engineering and a gastroenterologist at Brigham and Women's Hospital, are the senior authors of the study, which appears in Nature Medicine. The lead authors of the paper are recent MIT PhD recipient Alex Abramson and former MIT postdoc Ester Caffarel-Salvador.
The team previously developed a small capsule containing a small needle made of compressed insulin. When it reaches the stomach, the needle injects the drug into the stomach lining. In the new study, the researchers set out to develop a capsule that could inject its contents into the wall of the small intestine.
According to Traverso, most drugs are absorbed through the small intestine, in part because of its large surface area of around 250m2. 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.
According to MIT, each arm contains patches of 1mm long microneedles that can carry insulin or other drugs. When the arms unfold, 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 said in a statement.
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 30mm 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.