Technology that seems like it’s more out of the movie Ant-Man than from a university-based research lab is working on a new kind of smart insulin patch to treat diabetes.
Researchers at the University of North Carolina and North Carolina State announced they have developed a patch that, in a study on mice, detects blood sugar increases and then delivers insulin in response. The penny-sized patch is embedded with more than one hundred tiny needles, each about the width and length of an eyelash. Those needles in turn are loaded with microscopic storage units containing insulin and glucose-sensing enzymes that trigger a release of insulin when blood sugar levels go past a certain level.
“As a concept, it doesn’t get a whole lot better than this,” says Dr. John Buse, co-senior author of the results of a study on the patch published in the Proceedings of the National Academy of Sciences and the director of the UNC Diabetes Care Center. “As a physician, I admit, I was stunned by this.”
The “this” to which he refers was masterminded by co-senior author of the study, Dr. Zhen Gu, professor in the Joint UNC/NC State Department of Biomedical Engineering. Gu sought to develop a system that did not have to rely on mechanical devices using a sensor to read blood sugar levels then using a pump to deliver insulin when needed. Like insulin injections, Buse said that mechanical sensor and pump system can be imprecise, delivering too much or too little insulin and resulting in episodes of high or low blood sugar.
Instead Gu looked at how the body naturally did its job of reading blood sugar levels and then delivering insulin based on that reading. In particular, Gu and his team sought to emulate the way in which beta cells work in people without diabetes.
Healthy beta cells have a unique dual function of acting both as a sensor and a storage unit for insulin. They produce and store insulin in microscopic pouches called vesicles. The team then designed and built artificial vesicles, using materials found in nature instead of artificial, or mechanical materials.
“The first material was hyaluronic acid or HA, a natural substance that is an ingredient of many cosmetics,” according to a news release from UNC Health Care and School of Medicine. “The second was 2-nitroimidazole or NI, an organic compound commonly used in diagnostics. The researchers connected the two to create a new molecule, with one end that was water-loving or hydrophilic and one that was water-fearing or hydrophobic. A mixture of these molecules self-assembled into a vesicle, much like the coalescing of oil droplets in water, with the hydrophobic ends pointing inward and the hydrophilic ends pointing outward.”
Buse said that while the two materials have long been known, and while micro-needles have long been applied in other medical contexts, putting them together was a real breakthrough. In experiments, when blood sugar levels in mice went up the extra glucose flooded into the vesicles. Enzymes implanted into the vesicles then converted that sugar into gluconic acid, while also consuming oxygen. Once the oxygen ran out, the molecules fell apart and released insulin.
“It’s very clever,” Buse said, “especially in the way in which is mimics nature.”
Once the vesicles worked, the team had to make a decision how to deliver. Deciding that a catheter approach of using a needle implanted under the skin (much like those used in insulin pumps) to house the vesicles would not be as effective as they would want, Gu invented the system of micro-needles and put them on a patch.
The team “arranged more than one hundred of these micro-needles on a thin silicon strip to create what looks like a tiny, painless version of a bed of nails,” the release from UNC said. “When this patch was placed onto the skin, the micro-needles penetrated the surface, tapping into the blood flowing through the capillaries just below.
To test how the patch worked researchers tested one set of mice with type 1 diabetes with elevated glucose readings by giving them a standard insulin shot. In those mice blood glucose levels dropped but then, after some time, rose again to high levels. In another set of mice the same researchers applied the patch and found that blood sugar levels were brought within a normal ran after a half-an hour and that the levels remained normal for several hours afterward.
According to Gu, when the patch is fully developed it should last for several days before needing replacement.
The results are encouraging, but Buse cautions that, “just because it worked really well in mice doesn’t necessarily mean it will work well in anything else.”
He estimated that the technology might be ready for human clinical trials in two to five years.
“There’s still a ton of experiments that need to be done,” Buse said about the project, in which $2 million has already been invested. “At this time, however, we are very encouraged about where this is going.”