An international team of researchers from the United States, Denmark and Sweden has pioneered a new approach that brings an oral formulation of insulin that can be swallowed rather than injected one step closer to the clinic. The scientists have developed an ingestible microneedle that can inject insulin into the stomach lining in a large animal model. They have also demonstrated that their tiny pill — about the size of a blueberry — can be adapted to deliver other protein drugs.
Abramson et al developed a drug capsule that could be used to deliver oral doses of insulin. Image credit: Felice Frankel.
For almost a century, patients with diabetes have relied on injectable insulin to manage their condition. And for nearly as long, researchers have pursued a way to orally administer insulin.
While insulin injections can be lifesaving, they are unpleasant, cumbersome and increasingly expensive for patients, so health care providers often delay prescribing insulin injections in favor of less effective oral medications.
“We are really hopeful that our capsule could someday help diabetic patients and perhaps anyone who requires therapies that can now only be given by injection or infusion,” said MIT Professor Robert Langer, co-lead author of the study.
Several years ago, Professor Langer and colleagues developed a pill coated with many tiny needles that could be used to inject drugs into the lining of the stomach or the small intestine.
For the new capsule, the researchers changed the design to have just one needle, allowing them to avoid injecting drugs into the interior of the stomach, where they would be broken down by stomach acids before having any effect.
The tip of the needle is made of nearly 100% compressed, freeze-dried insulin, using the same process used to form tablets of medicine. The shaft of the needle, which does not enter the stomach wall, is made from another biodegradable material.
Within the capsule, the needle is attached to a compressed spring that is held in place by a disk made of sugar. When the capsule is swallowed, water in the stomach dissolves the sugar disk, releasing the spring and injecting the needle into the stomach wall.
The stomach wall has no pain receptors, so the scientists believe that patients would not be able to feel the injection.
To ensure that the drug is injected into the stomach wall, they designed their system so that no matter how the capsule lands in the stomach, it can orient itself so the needle is in contact with the lining of the stomach.
“As soon as you take it, you want the system to self-right so that you can ensure contact with the tissue,” said co-lead author Dr. Giovanni Traverso, a researcher at Brigham and Women’s Hospital, Harvard Medical School and MIT.
In tests in pigs, the scientists showed that they could successfully deliver up to 300 micrograms of insulin.
More recently, they have been able to increase the dose to 5 milligrams, which is comparable to the amount that a patient with type 2 diabetes would need to inject.
After the capsule releases its contents, it can pass harmlessly through the digestive system.
The researchers found no adverse effects from the capsule, which is made from biodegradable polymer and stainless steel components.
“Our self-orienting millimeter scale applicator (SOMA) worked only in animals in a fasted state,” they noted.
“Further research will be required to determine the chronic effects of daily gastric injections.”
“While additional study is needed, the SOMA represents a platform with the potential to deliver a multitude of drugs. Our results are encouraging and justify further evaluation of this technique for the oral delivery of insulin and other drugs,” Dr. Traverso said.
The team’s work appears in the journal Science.
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Alex Abramson et al. 2019. An ingestible self-orienting system for oral delivery of macromolecules. Science 363 (6427): 611-615; doi: 10.1126/science.aau2277
