Changing the way we take medicine

Swallowing a needle might not sound like good medical advice — but this odd concept may change the way many illnesses are treated.

An insulin injection pill equipped with a microneedle mechanism may be the future of Type 1 diabetes treatment, thanks to Dr. Robert Langer and his research team.

Langer is a recipient of both the National Medal of Science and National Medal of Technology and Innovation, Langer’s use of nanomedicine to treat disease has impacted 2 billion lives. He also holds more than 1,000 patents, has launched two-dozen startups and is a professor at MIT.

Langer and his team are also working on long-acting vaccine and medicine delivery systems, involving ingestible technology with timed release mechanisms to administer drugs at a specific time. These drugs, including a malaria treatment, are being developed for use in developing countries where limited access to healthcare keep people from getting recurring doses of medicine they need.

“What we felt we needed to come up with [was] a way to have somebody swallow something to [receive an] injection,” Langer said of the conceptualization for the design of the insulin pill.

One researcher in Langer’s lab, gastroenterologist Giovanni Traverso, saw the stomach as the ideal injection sight.

“Of course, you need [that] something to always be facing exactly the right place in the stomach. So, we needed to have some kind of self-righting mechanism,” added Langer.

The insulin pill is triggered by water taken with the pill to release the insulin injection at a set time in the stomach.

The next challenge for the team was how to make such a pill – one equipped with a needle – broadly appealing.

For Traverso swallowing a needle of this size raised no concerns. “With patients who have inadvertently or intentionally ingested sharp objects … if that sharp object is small enough, the likelihood of there being any complication drops dramatically,” he said. “For objects that are approximately under a centimeter, the risk of injury is very low, and it really drops precipitously after that.”

This means an injection in the stomach is not only relatively harmless and painless, but it also allows the injected treatment to circulate throughout the body very quickly.

According to Traverso, the clinical observations about the advantages of injecting insulin through the stomach – a location that allows doctors to “rapidly see a systemic response” – affirmed the team’s plan for the pill.

Drawing this kind of conclusion was born out of the nature of Langer’s lab. Langer’s lab encourages and thrives on interdisciplinary work, with researchers from diverse scientific backgrounds including chemical engineers, pharmaceutical scientists, physicians, veterinarians, and electrical engineers.

“Bob’s approach, something he’s been doing now for over 40 years, has been to try and foster an interdisciplinary environment and groups of people to work together to try and solve major challenges,” Traverso said. “About 11 years ago now, I met Bob and I was interested in doing my fellowship research with him at the time. I told him I didn’t really know much about chemical engineering or biomedical engineering but I wanted to learn. I was a gastroenterologist and molecular biologist,” Traverso said. Langer welcomed him and his unique perspective to the research team, which encourages interdisciplinary work.

“One of the things he says is that getting people who are not working in this field to really think about this field [means] that they are not burdened by all of the prejudices of the field,” Traverso added. “Bringing a fresh view can  be really impactful.”

Langer has brought fresh ideas to the longstanding problem of malaria treatment. The standard treatment requires a patient to take 24 tablets over the course of three days, every eight hours.

“The crux of the problem is adherence. This is a huge problem,” Traverso said.

“It’s fairly burdensome pill load, [which needs to be] spaced at the right time to ensure that folks actually receive the right treatment,” Traverso added. “[Doing that correctly] with a single administration treatment could potentially transform how folks receive it. It could also ensure people receive it in a safe and efficacious way.”

To improve upon this complicate treatment regiment, Langer and his team developed an ingestible technology that expands into a star shape in the stomach. There it administers the multiple doses of treatment before dissolving and passing through the gastrointestinal tract.

“The interesting thing about that shape is that it can’t get past the pylorus, the little hole between your stomach and intestine,” Langer said. “It so big it can’t get past it, but it’s open [enough that] food can pass – it doesn’t block anything.”

Thanks to advanced polymer chemistry, “we can tune its degradation. We can make it last a week, a month or a year. We can have it, while it’s sitting there, release whatever drug we want,” Langer added.

While both treatments are still in development, they offer potential to treat a variety of conditions that require daily doses or does that must be taken at specific times.

“You never know when you come up with science where it’s going to take you,” Langer said of these emerging technologies, whose potential applications are vast and varied. “It’s a platform technology that I hope can be used for anything,” Langer said. “Of course, a lot more needs to be done in terms of safety.”

Langer said the long-acting pill could also be developed to administer AIDs treatment, including three drugs with one pill lasting a week. The technology could also help with conditions where the ailment itself creates difficulty in managing proper dosing, including schizophrenia and Alzheimer’s.

The long-acting pill is expected to begin Phase II trials next year, which are required for approval in the United States. And before patients can begin using the insulin pill, more studies will need to be conducted to test efficacy and dosing in non-human primates. So far, the treatment has been tested in pigs and smaller animals.

“Our hope is [for] more funding, and that clinical trials might start in the next several years,” Langer said.