Pills are less uncomfortable than injections for most people. However, some drugs only work when injected. Researchers have now developed a capsule that could provide a remedy: Thanks to a clever design, it aligns itself in the stomach after swallowing and uses a tiny needle to pinch the active ingredient into the gastric mucosa. Preclinical tests on pigs showed promising results.
Many people with diseases such as Crohn’s disease, rheumatoid arthritis, or diabetes need regular injections or IV fluids to keep their symptoms under control. For many of those affected, the frequent injections are stressful and limit their quality of life. It would be easier and more pleasant for them to swallow a tablet instead. However, drugs such as insulin, epinephrine or monoclonal antibodies, whose effects are based on large proteins, cannot yet be administered orally. They would be broken down in the gastrointestinal tract before they can be absorbed into the body.
Injections for swallowing
A team led by Alex Abramson from the Massachusetts Institute of Technology (MIT) in Cambridge has now developed an approach that could nevertheless make it possible to take these drugs orally. The researchers have developed a swallowable capsule that injects active ingredients into the lining of the stomach. At 12 by 15 millimeters, the pill is about the size of a blueberry. The shape resembles a steeply curved turtle shell. “This self-aligning geometry ensures that the capsule rotates in the stomach so that the injection side is always directed towards the gastric mucosa – similar to a wobbly toy that keeps popping up by itself,” the researchers explain.
“The design ensures that the capsule delivers the dose into the tissue and not into the stomach cavity. This bypasses the enzymatic breakdown that takes place in the stomach. ”Inside the capsule, which the researchers called L-SOMA (liquid-injecting self-orienting millimeter-scale applicator), is the liquid active ingredient and an injection mechanism. Before the capsule gets into the stomach, the needle is held in place with a pellet of solid sugar. Upon contact with stomach acid, the pellet quickly dissolves, releasing a spring mechanism that pushes the needle out of the capsule and into the tissue. Another mechanism ensures that the active ingredient is injected. After the injection, the needle retracts into the capsule and the capsule can be excreted.
Bioavailability is similar to that of syringes
The researchers tested their new system on pigs. To do this, they administered the capsule to the anesthetized animals directly into the stomach using an endoscope and observed how it moved there and released its active ingredient. For the tests, Abramson and his colleagues used four different drugs that usually have to be injected: the insulin, which is important for diabetics, epinephrine, which is used, among other things, for asthma, the monoclonal antibody adalimumab, which acts against autoimmune diseases such as rheumatoid arthritis and Crohn’s disease, and a GLP-1 analog, which is also used in diabetes.
“A total of 28 of 31 of the pigs treated with L-SOMA absorbed the active ingredient systemically,” report the researchers. In the three cases where the uptake failed, either the capsule’s injection mechanism was malfunctioning or the drug was injected but not absorbed into the bloodstream. In all other cases, the drugs administered with L-SOMA showed just as high a bioavailability as when the corresponding active ingredients were injected under the skin or into a muscle.
Diverse application possibilities conceivable
In addition, Abramson and his colleagues examined the extent to which L-SOMA might damage the stomach. “Some animals had a small amount of gastric mucosal bleeding after administration, but this stopped within a few minutes and left no permanent traces,” they report. This also applied to pigs that were given L-SOMA repeatedly over a period of three days. Tissue samples from euthanized animals also showed at most minor abnormalities, some of which were also due to the endoscope. “Overall, the results show that L-SOMA causes minimal, if any, tissue damage that heals quickly,” the researchers say.
Still, the researchers emphasize that future human clinical trials will focus on safety. While the pigs received the capsule through an endoscope, human patients would swallow L-SOMA like a normal tablet. The researchers have already demonstrated with dogs that this works in principle.
“We now know that tablets are the preferred route of drug delivery, not just for patients but also for healthcare providers,” said Abramson’s colleague Giovanni Traverso. It would also be conceivable in the future, for example, to administer vaccines with the help of L-SOMA. “Although we are still at the beginning, we believe this device has the potential to change treatment methods in a number of therapeutic areas,” says co-author Ulrik Rahbek of the Danish pharmaceutical company Novo Nordisk, which is involved in the development. “The ongoing research into this approach means that several drugs that can currently only be administered via injections could also be administered orally in the future. Our goal is to bring the device to clinical trials as soon as possible. “
Source: Alex Abramson (Massachusetts Institute of Technology, Cambridge, USA) et al., Nature Biotechnology, doi: 10.1038 / s41587-021-01024-0