You probably don’t spend a lot of time wondering just how hard your stomach works to break down your grub. Food goes in, waste goes out, and if everything’s working as it should, you probably don’t give it much thought.
But inside the stomach is a highly acidic environment; this quality is crucial to break down food and provides some protection against some bacteria or other pathogens that might crawl their way into our food.
Intestinal microbiota and degradative enzymes further break down food particles — together, this symphony of decomposition helps us absorb the nutrients we need and eliminate whatever we don’t.
But our internal decomposition machine isn’t always helpful. For instance, it can pose a challenge for oral medications just trying to do their job.
The digestive system is designed to break things down and block anything that doesn’t seem like it should be in the gut from being absorbed into the intestines; developing drugs that can remain stable in that ecosystem can be tricky. It’s why some medications like insulin are injected subcutaneously, which can be burdensome and unpleasant for some people.
But what if a robotic device could avoid the decomposition obstacles mounted by the digestive system and deliver medications directly into the (small) intestines where they’re 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 accomplished exactly that. The results of their preclinical tests of the device, named RoboCap, were published Wednesday in the journal Science Robotics.
Here’s the background — For a drug to reach the intestines, where it can finally be absorbed into the bloodstream, it faces a series of challenges.
Along with surviving the stomach’s harsh acidic environment and remaining stable among intestinal bacteria, the medication has to “evade the efflux pumps, which are special proteins that literally try to push things back out into the small intestine,” according to Shriya Srinivasan, a researcher at MIT and first author on the study.
Perhaps the biggest obstacle: “This thick mucus layer sitting right on top of all the cells where a lot of drugs simply get trapped and don't make it to the small intestine,” she says.
After the mucus layer, drugs encounter intracellular tight junctions, which are tiny spaces designed to keep out dangerous pathogens. Some substances that have a particularly hard time clearing that mucus layer, like insulin and an antibiotic called vancomycin, are comprised of molecules too big to fit through those tight junctions.
In some cases, Srinivasan says, “only some of the molecules will make it through and become absorbed in the bloodstream, and the rest gets 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 the drug travels safely through the stomach, whizzes past the mucus barrier, and slides 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 her colleagues set out to invent that very system.
What they did — Srinivasan says she had her eureka moment while watching videos on tunnel-digging machines that connected the U.K. to Europe underground.
“I thought, how interesting, what if we can do this to tunnel through mucus,” she says. That’s how she and her colleagues conceived the “rollover path” on the RoboCap, which has a motor, batteries, and electronic components encased in a gelatin capsule, which is around the size of a large multivitamin.
The pH of the small intestine then activates the RoboCap’s turbine fins that essentially push off pointy structures in the small intestine called villi that absorb nutrients. Then, the capsule’s little studs grab the mucus and brush it off.
This allows the RoboCap to pass the mucus and drop off the drug right on the epithelium, where it can be fully absorbed.
Finally, the body eliminates the rest of the RoboCap as waste.
What they found — In a swine model, the RoboCao made vancomycin 20 to 40-fold more absorbable compared to a standard pill delivery method. For insulin, the bioavailability increased more than 10-fold compared to a standard oral delivery method.
“When we give insulin to animals orally, there's very little uptake,” Srinivasan says. “The blood glucose barely changes. If we give through the RoboCap, you get a significant decrease [in blood glucose]. “This means that instead of patients using insulin injections, they might be able to take it orally.”
What’s next — While more testing needs to happen to ensure the safety and efficacy of the RoboCap, these preclinical trials seem promising.
Srinivasan says she understands that some may be hesitant to swallow anything with a battery, but “the electromechanical components are sealed off in such a way that even if you were to submerge it for many, many weeks, it's not only that you're not going to have any 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 are hoping to partner with a pharmaceutical company that could help take their research to clinical trials. She thinks this kind of device could certainly appeal to the industry.
“A lot of drugs and millions of dollars go to waste every year because [drug trials] get to the very final stages, and they actually work at the cellular level. But by the time you put them through the gamut of challenges that they need to go through to actually be absorbed, they don't make it.”
That’s a pricey problem that has harmful health consequences globally. But, with a little luck and many successful trials, the plucky little RoboCap could help solve it.