probably not spend a lot of time wondering how hard your stomach is working to break down your food. Food goes in, waste goes out, and if everything works as it should, you probably don’t give it much thought.
But inside the stomach there is a highly acidic environment; this quality is crucial for breaking down food and provides some protection against some bacteria or other pathogens that might find their way into our food.
Gut microbiota and degradative enzymes further break down food particles; Together, this symphony of decomposition helps us absorb the nutrients we need and eliminate what we don’t.
But our internal breakdown machine is not forever Useful. For example, it can present a challenge to oral medications that are just trying to do their job.
The digestive system is designed to break things down and block anything that doesn’t look like it should be in the gut from being absorbed by the intestines; developing drugs that can remain stable in that ecosystem can be tricky. This is why some medications such as insulin are injected subcutaneously, which can be uncomfortable and unpleasant for some people.
But what if a robotic device could bypass the breakdown hurdles mounted by the digestive system and deliver drugs directly into the (small) intestine where they are most likely to be absorbed?
It may seem out of this world, but researchers at the Massachusetts Institute of Technology and Brigham and Women’s Hospital at Harvard Medical School in Boston may have achieved just that. The results of their preclinical testing of the device, called RoboCap, were published Wednesday in the journal Robotic Science.
here is the background — Getting a drug into the intestines, where it can ultimately be absorbed into the bloodstream, faces a number of challenges.
In addition to surviving the harsh acidic environment of the stomach and remaining stable among gut bacteria, the drug has to “evade efflux pumps, which are special proteins that literally try to push things into the small intestine,” according to Shriya Srinivasan, a researcher at MIT and first author of the study.
Perhaps the biggest hurdle: “This thick layer of mucus that sits right on top of all the cells where a lot of drugs just get trapped and don’t make it to the small intestine,” she says.
After the mucus layer, the drugs encounter intracellular tight junctions, which are tiny spaces designed to keep out dangerous pathogens. Some substances that have a particularly difficult time removing that layer of mucus, such as insulin and an antibiotic called vancomycin, are made up of molecules too large to fit through those tight junctions.
In some cases, says Srinivasan, “only some of the molecules will make it through and be absorbed into the bloodstream, and the rest will be eliminated.” That’s not only inefficient, it’s expensive. “If you’re taking 10 molecules of something and only one makes it through, you’re still paying for the other nine,” she says.
But a high-tech delivery system could ensure that the drug travels safely through the stomach, crosses the mucosal barrier and slips into the bloodstream. This could achieve more cost-effective targeted dosing and allow for more oral medications that are easier for patients to administer.
Srinivasan and his colleagues set out to invent that very system.
What did you do – Srinivasan says he had his eureka moment while watching videos about tunneling machines connecting the UK with Europe underground.
“I thought, how interesting, what if we could do this to tunnel through mucus,” she says. That’s how she and her colleagues conceived of the “rollover road” in the RoboCap, which has a motor, batteries, and electronics encased in a gelatin capsule the size of a large multivitamin.
The pH of the small intestine then activates the RoboCap’s turbine blades which essentially push spiky structures in the small intestine called villi that absorb nutrients. Then the little studs on the capsule grab the mucus and brush it away.
This allows RoboCap to pass through mucus and drop the drug directly into the epithelium, where it can be fully absorbed.
Finally, the body disposes of the rest of the RoboCap as waste.
What they found – In a pig model, RoboCao made vancomycin 20 to 40 times more absorbable compared to a standard pill delivery method. For insulin, bioavailability increased more than 10-fold compared to a standard oral delivery method.
“When we give animals insulin orally, there is very little absorption,” says Srinivasan. “Blood glucose barely changes. If we give through the RoboCap, a significant decrease is obtained [in blood glucose]. “This means that instead of patients using insulin injections, they could take it orally.”
Whats Next – While more testing is needed to ensure the safety and efficacy of RoboCap, these preclinical trials show promise.
Srinivasan says he understands that some may be hesitant to swallow anything with a battery, but “the electromechanical components are sealed in such a way that even if you had to submerge them for many, many weeks, it’s not just that you’re not going to have negative effects. In some of the animals, it was present for seven to 10 days inside the system. We still didn’t see any negative side effects.”
She and her colleagues hope to partner with a pharmaceutical company that could help take their research into clinical trials. She thinks this type of device could certainly appeal to the industry.
“Many drugs and millions of dollars are wasted every year because [drug trials] they reach the final stages, and they actually work at the cellular level. But when you put them through the range of challenges that they need to really absorb, they don’t make it.”
That’s a costly problem that has damaging health consequences globally. But, with a bit of luck and a lot of successful testing, plucky little RoboCap might just be able to help figure it out.