Researchers in the US have designed an implantable reservoir that can remain under the skin and be triggered to release glucagon when type 1 diabetes patients’ blood sugar levels get too low.
The device could acts an emergency backup for cases where patients may not realise that their blood sugar is dropping to dangerous levels,
This approach could also help in cases where hypoglycemia occurs during sleep, or for diabetic children who are unable to administer injections on their own.
Daniel Anderson is 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.
The researcher said: “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.
“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.”
The researchers showed that this device could also be used to deliver emergency doses of epinephrine, a drug that is used to treat heart attacks and can also prevent severe allergic reactions, including anaphylactic shock.
Most patients with type 1 diabetes use daily insulin injections to help their body absorb sugar and prevent their blood sugar levels from getting too high.
However, if their blood sugar levels get too low, they develop hypoglycemia, which can lead to confusion and seizures, and may be fatal if it goes untreated.
To combat hypoglycemia, some patients carry preloaded syringes of glucagon, a hormone that stimulates the liver to release glucose into the bloodstream.
However, it isn’t always easy for people, especially children, to know when they are becoming hypoglycemic.
To make it easier to counteract hypoglycemia, the MIT team set out to design an emergency device that could be triggered either by the person using it, or automatically by a sensor.
The device vontains a small drug reservoir made of a 3D-printed polymer.
The reservoir is sealed with a special material known as a shape-memory alloy, which can be programmed to change its shape when heated.
In this case, the researcher used a nickel-titanium alloy that is programmed to curl from a flat slab into a U-shape when heated to 40 degrees Celsius.
Like many other protein or peptide drugs, glucagon tends to break down quickly, so the liquid form can’t be stored long-term in the body.
Instead, the MIT team created a powdered version of the drug, which remains stable for much longer and stays in the reservoir until released.
Each device can carry either one or four doses of glucagon, and it also includes an antenna tuned to respond to a specific frequency in the radiofrequency range.
That allows it to be remotely triggered to turn on a small electrical current, which is used to heat the shape-memory alloy.
When the temperature reaches the 40-degree threshold, the slab bends into a U shape, releasing the contents of the reservoir.
Because the device can receive wireless signals, it could also be designed so that drug release is triggered by a glucose monitor when the wearer’s blood sugar drops below a certain level.
Siddharth Krishnan is a former MIT research scientist who is now an assistant professor of electrical engineering at Stanford University.
Krishnan said: “One of the key features of this type of digital drug delivery system is that you can have it talk to sensors.
“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.”
After implanting the device in diabetic mice, the researchers used it to trigger glucagon release as the animals’ blood sugar levels were dropping.
Within less than 10 minutes of activating the drug release, blood sugar levels began to level off, allowing them to remain within the normal range and avert hypoglycemia.
The researchers also tested the device with a powdered version of epinephrine.
They found that within 10 minutes of drug release, epinephrine levels in the bloodstream became elevated and heart rate increased.
In this study, the researchers kept the devices implanted for up to four weeks, but they now plan to see if they can extend that time up to at least a year.
Image: MIT