Patches and robotic pills could one day replace injections

Do you hate getting shot? If so, you’re not alone – and you might be lucky. Researchers are designing new, painless ways to deliver drugs. One is a robotic pill. Another is a medical patch worn on the skin. Both are still in the early stages of development. But one day, these innovations could make drug delivery more patient-friendly.

The new robotic pill comes out of a lab at the Massachusetts Institute of Technology in Cambridge. It contains a tiny spring-loaded micro-needle about 3 millimeters (one tenth of an inch) long. Once swallowed, the pill injects the drug directly through the stomach wall.

Unlike a normal shot, this needle stick shouldn’t hurt, says Giovanni Traverso. He is a doctor and a biomedical engineer specializing in the intestine. He also helped develop the robo-pill at MIT. Stomachs can detect certain sensations, such as the deep pain of a stomach ulcer. Or the discomfort of feeling bloated. But these sensations are “more related to the stretch receptors,” says Traverso. The stomach lacks receptors to detect sharp pains, such as an injection.

This little robotic pill can deliver medicine into your stomach with a micro-needle that comes out at the right time.G.Traverso

Designing a pill that could reliably prick the stomach wall was a bit tricky. Once swallowed, the small but heavy device settles at the bottom of the stomach. In order to puncture the stomach wall below, the pill must land injector side down. To get there, the MIT team borrowed an idea from the leopard tortoise.

Contrary to popular belief, most turtles can get back on their feet if knocked down. Leopard tortoises are aided by strongly domed shells. If one of them is turned over on its back, the shape of this shell helps it roll upright. This same shape ensures that the new pill always lands upright as well.

Robert Langer is a chemical engineer in the MIT team. “Look,” he said, dropping a chickpea-sized robotic pill onto a table. It bounces, then rolls upright. “No matter how I drop it,” he notes – and he drops it again – “it always lands the same way.”

But what gets the little needle out of the pill to do its job? “Glass of sugar,” says Langer. Hard and brittle, this material retains a spring which is attached to the needle. In the stomach, this sugar begins to dissolve. “All of a sudden the thing breaks,” Langer says. This releases the spring, which pushes the needle into the stomach wall to inject the medicine. It is possible to control when this happens by adjusting the thickness of the sugar.

The MIT team unveiled its design in 2019 in Science.

a photo of a leopard tortoise
The shape of this leopard tortoise’s shell ensures that the animal rolls right side up if it rolls over onto its back. This hull inspired the shape of the new robo-pill.David A. Northcott /iStock/Getty Images Plus

Potential benefits and prices

In new experiments, these robotic pills have delivered an mRNA-based drug to mini-pigs. The researchers described their success in the March 2 issue of Question. This was an important test to show that this new class of drugs could be delivered in this way. (Pfizer’s COVID-19 vaccine also relies on mRNA.)

The new robo-pills also succeeded insulin delivered in mini-pigs. Many people with diabetes need to inject themselves with this hormone several times a day. Normally, insulin cannot be swallowed in pill form because it will break down in the stomach. The robo-pill gets around this problem by feeding insulin directly into the stomach wall.

It’s a whole new way of delivering the drug, notes Bruno Sarmento. He works at the University of Porto in Portugal. Although he has not worked on the pill system, as a nanomedicine researcher he is interested in such projects. “We now know it’s possible” for a robotic system to reach into the stomach and administer injections, he says. But he fears the new pill will be too expensive for widespread use.

Starting at 50 seconds in this video, you can see an explanation of how a self-righting turtle shell served as the inspiration for a new capsule-based system for releasing insulin. Animal tests show that its micro-needles can quickly release the hormone into the stomach lining.

Langer is not so sure. “Actually, I don’t know if it will be that expensive,” he says. Mechanized pills already exist. Langer points to a class known as osmotic pills. These pills have holes for pumping medicine. People might think they would be much more expensive than regular pills, “but that’s really not the case,” he says. “When you start making billions of them, the cost just goes down.”

In addition, normal pills often waste medicine. A swallowed drug must pass through the stomach lining. “It’s like walking through a brick wall,” says Traverso. It is very difficult without the aid of a needle. And wasted drugs are expensive – “sometimes more expensive than the device”.

An example is a drug used to treat diabetes. This is called semaglutide. “It’s a giant seller for people with diabetes,” Langer says. And when you give this drug in pill form, he says, “you lose 99% of the drug.” It passes through the body before being absorbed. But the new robotic pill would ensure that the drug passes through the stomach wall and enters the bloodstream. In the end, it could save money.

After successful animal testing, the robot pill is now ready for human trials. Danish pharmaceutical company Novo Nordisk, which is working with the MIT team, began recruiting volunteers in April.

Patch the skin

Researchers in France are developing a technology that skips the needles completely. The team’s new patch, when applied in the mouth, delivers medicine to the inside of the cheek.

“Needle-free injections… it’s sort of the holy grail,” says Karolina Dziemidowicz. She did not help create the new patch. But his work in England at University College London focuses on these new biomaterials.

a photo of a small black diamond-shaped patch on the fingertip
This tiny, heat-activated patch can deliver insulin through the skin inside your cheek.Anna Voronova

Drug-laden sticky patches have been around for decades, Dziemidowicz notes. This new one is different. Rather than sticking it to your arm, it goes on the slippery, mucus-covered membrane inside your mouth. Or even your eyeball! Both are areas that allow drugs to quickly enter your bloodstream. Gentle heat from a laser device activates the patch to release the medication.

Sabine Szunerits is an analytical chemist and co-developer of these tiny patches. She works at the University of Lille in France. His team tested these patches as a way to deliver insulin. Like the MIT team, they tried their system on mini-pigs – and later, on cows. The animals absorbed the drug well and reduced their blood glucose levels as expected.

In another experiment, the researchers even applied drug-free versions of the patches to the mouths of six volunteers. What did people think of them? It’s weird to think about, said two male volunteers. But no one found the patches uncomfortable. The patches also did not affect the volunteers’ ability to speak or eat.

Szunerits and his team described their findings in Applied Biological Materials ACS February 21.

New technology, new things to consider

In their laboratory, the French team used a laser to make the patch release its drug. For home use, Szunerits imagines creating something like a pacifier. In the end, she said, “you would have a laser.” Then, when you’re ready to activate a patch, you place the laser-pop in your mouth. You can trigger just one – or as many patches as needed to take the prescribed dose.

“It’s a very elegant study,” Sarmento says. But he sees a limit there. The patches cannot deliver much insulin. Each can pack about 2.9 units of medicine. But even a 40 kilogram (90 pound) child may need about 20 units of insulin a day. Sarmento suspects the new patch might be better suited to other drugs, those given in lower doses.

The patches are small, but some people might be willing to wear a bunch if it means avoiding an injection. People, especially children, don’t like beatings. Because of this, says Traverso, many people only reliably take their insulin about half the time. That’s why many “doctors delay starting insulin for almost eight years,” says Traverso.

He now hopes that innovations such as the insulin patch and the robotic pill will one day inspire more people to voluntarily take the drugs they need.

This is part of a series featuring news on technology and innovation, made possible through the generous support of the Lemelson Foundation.