Researchers at Brigham and Women's Hospital, Massachusetts Institute of Technology and Novo Nordisk have revealed the new self-injecting capsule, called the liquid-injecting self-orienting millimeter-scale applicator (L-SOMA) that administers typically injected liquid medications orally.
While injections help people who suffer from diseases such as Crohn’s disease, rheumatoid arthritis, and diabetes, these injections require training, equipment and are often inconvenient for those who need them. Most large protein drugs, however, cannot usually be given orally because enzymes in the digestive tract break them down before they can be absorbed.
"We recognize today that pills are the preferred route of drug administration, not only for patients, but also for health care providers. If we can make it easier for patients to receive their medication, we can help maximize drug adherence or compliance," said C. Giovanni Traverso, MB, BChir, PhD, of the Division of Gastroenterology, Hepatology and Endoscopy at the Brigham and the Department of Mechanical Engineering at MIT. "Our group focuses on developing systems that make it easier for patients to receive their medications."
Targeting diabetes, Crohn's disease and others
The researchers used the tech to deliver four commonly injected medications in a study published in Nature Biotechnology. The four medications were insulin, epinephrine, adalimumab (a monoclonal antibody used to treat rheumatoid arthritis, Crohn’s disease and other autoimmune diseases) and a semaglutide-like GLP-1 analog (an anti-diabetic medication).
The pill contains a retractable needle that injects the treatment directly into tissue within the stomach. After the L-SOMA delivers the drug, the needle retracts back into the capsule and the capsule is excreted through the digestive tract.
The tech is based on an invention revealed in 2019 – the SOMA – which injects solid medications (it was tested with insulin) but does not work with liquid drugs. The upgraded L-SOMA device has been designed to work with liquid medications that need to be absorbed more quickly or are challenging to formulate as solids.
The capsule is filled with fluid and also contains an injection needle and a plunger that helps to push the fluid out of the capsule. Both the needle and plunger are held in place by a pellet made of solid sugar. When the capsule enters the stomach, the humid environment causes the pellet to dissolve, pushing the needle into the stomach lining, while the plunger pushes the liquid through the needle. When the capsule is empty, a second plunger pulls the needle back into the capsule so that it can be safely excreted through the digestive tract.
The pill is about the size of a blueberry, with a ‘high, steep dome inspired by the leopard tortoise’. It targets the stomach, rather than later parts of the digestive tract, because the time taken to reach the stomach is most predictable, while the lining of the stomach is thick and muscular.
Further potential with vaccines
The study tested the pill in pigs, collecting blood samples from each of the animals and finding that medications were delivered at comparable levels to injection. They also found that repeated treatments with the L-SOMA dosed with insulin induced the same results, suggesting it may be effective to give multiple, subsequent doses using L-SOMA.
The pill was capable of delivering up to 4-mg doses of a bioavailable drug with the rapid pharmacokinetics of an injection, reaching an absolute bioavailability of up to 80% and a maximum plasma drug concentration within 30 min after dosing.
“This approach improves dosing efficiencies and pharmacokinetics an order of magnitude over our previously designed injector capsules and up to two orders of magnitude over clinically available and preclinical chemical permeation enhancement technologies,” notes the study.
The next move will be to test the technology in humans, with the researchers suggesting a wide range of injectable medicines and vaccines – including COVID-19 vaccines – could be potentially administered this way.
"Through the application of fundamental engineering, the type of drugs we can deliver orally is being transformed. It changes how we think about managing different conditions,” Traverso said. “This technological advancement could apply to chronic conditions that require regular dosing or to systems that are more episodic. Mass administration of an otherwise injectable drug also becomes much easier if it can be given orally."
The research was funded by Novo Nordisk, the National Institutes of Health, the National Science Foundation, MIT’s Department of Mechanical Engineering, Brigham and Women’s Hospital’s Division of Gastroenterology, and the Viking Olof Bjork scholarship trust.
Study: Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors, Nature Biotechnology (2021). https://doi.org/10.1038/s41587-021-01024-0