Microneedle capsule could deliver insulin and other protein-based drugs orally
Earlier this year we covered a blueberry-sized capsule developed by researchers at MIT that would allow diabetics to take their insulin orally rather than by injection. That capsule contained microneedles to deliver the hormone through the stomach lining. Now, the same team has gone a step further, developing a new capsule that would survive a trip through the stomach and deliver its payload to the lining of the small intestine.
The reason insulin and other protein-based drugs can't currently be taken orally is because they are broken down in the gastrointestinal tract before they can do their work. In an effort to change this, and reduce the need for frequent injections, Robert Langer, Giovanni Traverso and others have been spent years developing oral alternatives, including the aforementioned blueberry-sized capsule.
The team is also responsible for a number of other capsule technologies, including one from 2014 that is designed to make its way through to the small intestine, and a star-shaped assembly from 2016 that unfolds from its capsule container to release medication in the stomach over an extended period. This new capsule combines aspects of both of these.
Firstly, it is designed to survive the harsh, acidic environment of the stomach and reach the small intestine, which, unlike the stomach, doesn't have any pain receptors. Secondly, when it reaches the small intestine, the higher pH there triggers the capsule to spring open and release three arms that are folded inside. It is these arms that carry the drug payload in patches of 1-mm-long microneedles.
The force of the arms unfolding is enough for the microneedles to puncture the topmost layer of the small intestine tissue (the team has conducted tests on animal and human tissue to ensure the needles don't penetrate deeper than necessary). Then, as the microneedles dissolve, they release their drug payload for uptake into the bloodstream. Once this is accomplished, the arms break apart to reduce the chance of a blockage in the intestine.
"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," says Ester Caffarel-Salvador, a lead author on the study.
The researchers have tested 30-mm-long capsules on pigs and say that they effectively delivered doses of insulin, resulting in an immediate lowering of blood glucose levels. The pigs also experienced no intestinal blockages and the arms were safely excreted after the microneedle patches were applied to the wall of the intestine.
"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 Langer.
The "others" Langer is referring to is anyone requiring injections for the delivery of other protein drugs, such as hormones, antibodies, enzymes or 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."
The team's paper appears in Nature Medicine.