A new implantable device carries a reservoir of glucagon that can be stored under the skin and could save diabetes patients from dangerously low blood sugar. [Image courtesy of the researchers]
Researchers at MIT say they designed an implantable reservoir that releases glucagon when blood sugar levels get too low in people with diabetes.
For those with type 1 diabetes, hypoglycemia (low blood sugar) remains a life-threatening possibility. The researchers say they developed an implantable device that remains under the skin to combat this. When blood sugar levels get too low, they trigger the device to release glucagon. The approach could help in cases where hypoglycemia occurs during sleep or for diabetic children unable to administer injections on their own.
Currently, most patients with type 1 diabetes use daily insulin injections to prevent blood sugar levels from getting too high. Some patients carry preloaded glucagon syringes to combat hypoglycemia, but there are hurdles, according to a post on the MIT website.
“This is a small, emergency-event device that can be placed under the skin, where it is ready to act if the patient’s blood sugar drops too low,” says Daniel Anderson, a professor in MIT’s Department of Chemical Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES), and the senior author of the study. “Our goal was to build a device that is always ready to protect patients from low blood sugar. We think this can also help relieve the fear of hypoglycemia that many patients, and their parents, suffer from.”
Siddharth Krishnan, a former MIT research scientist who is now an assistant professor of electrical engineering at Stanford University, is the lead author of the study, which appeared today in Nature Biomedical Engineering.
The researchers sought to design an emergency device that can be triggered either by the person using it or automatically by a sensor. Coming in at the size of a U.S. quarter, the device contains a small drug reservoir made of a 3D-printed polymer. The researchers seal the reservoir with a shape memory alloy that can change its shape when heated. They used a nickel-titanium allow programmed to curl from a fat slab into a U-shape when heated to 40 degrees celsius.
According to MIT, glucagon often breaks down quickly, preventing long-term storage in the body. The researchers addressed this by creating a powdered version of the drug that remains stable longer and stays in the reservoir until released. Each device can carry either one or four doses of glucagon and has an antenna tuned to respond to a specific frequency in the radiofrequency range. That allows remote triggering to turn on a small electrical current and heat the alloy. When the temperature reaches 40 degrees, the slab bends and releases the contents of the reservoir.
Because the device can receive wireless signals, a wearable glucose monitor could also trigger the glucagon release. This isn’t dissimilar to existing automated insulin delivery systems that communicate with sensors, although none on the U.S. market are fully implantable.
“One of the key features of this type of digital drug delivery system is that you can have it talk to sensors,” said Krishnan. “In this case, the continuous glucose-monitoring technology that a lot of patients use is something that would be easy for these types of devices to interface with.”
The researchers implanted the device in diabetic mice to trigger glucagon release. Within less than 10 minutes of activating the release, blood sugar levels tailed off to bring the mice into the normal range and avoid hypoglycemia. With the mice, researchers kept the devices implanted for up to four weeks but aim to evaluate if they can extend that time up to at least a year.
“The idea is you would have enough doses that can provide this therapeutic rescue event over a significant period of time. We don’t know exactly what that is — maybe a year, maybe a few years, and we’re currently working on establishing what the optimal lifetime is. But then after that, it would need to be replaced,” Krishnan says.
Additionally, the researchers say that implantable devices can often have scar tissue develop around them and interfere. In the study, they saw that even when this happened, they could still trigger the drug release. They plan to conduct additional animal studies and begin clinical trials within the next three years.
The researchers also tested powdered epinephrine with the device. They found that within 10 minutes of drug release, epinephrine levels in the bloodstream became elevated and heart rate increased.
“It’s really exciting to see our team accomplish this, which I hope will someday help diabetic patients and could more broadly provide a new paradigm for delivering any emergency medicine,” says Robert Langer, the David H. Koch Institute Professor at MIT and an author of the paper.