Smart insulin patch could replace injections for diabetes

By John Murphy, MDLinx
Published December 23, 2015

Key Takeaways

Researchers have invented a “smart insulin patch” that detects increases in blood sugar levels and quickly secretes doses of insulin into the bloodstream whenever needed. If proven effective in humans, the smart insulin patch has the potential to replace bothersome insulin injections, according to researchers at the University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC.

The new, painless patch is smaller than a postage stamp and is covered with an array of more than 100 microneedles, each of which are loaded with insulin and glucose-sensing enzymes that rapidly release the insulin when blood sugar levels get too high.

Investigators found that the patch was able to lower blood glucose in mice with type 1 diabetes for up to 9 hours. Their study is published in the Proceedings of the National Academy of Sciences.

“We have designed a patch for diabetes that works fast, is easy to use, and is made from nontoxic, biocompatible materials,” said co-senior author Zhen Gu, PhD, a professor in the Joint UNC/NC State Department of Biomedical Engineering. Dr. Gu also holds appointments in the UNC School of Medicine, the UNC Eshelman School of Pharmacy, and the UNC Diabetes Care Center in Chapel Hill, NC. “The whole system can be personalized to account for a diabetic’s weight and sensitivity to insulin,” he added, “so we could make the smart patch even smarter.”

Because mice are less sensitive to insulin, the researchers think that the blood sugar-stabilizing effects of the patch could last even longer when given to human patients. The eventual goal, Dr. Gu said, is to develop a smart insulin patch that patients would only have to change every few days.

Other researchers have tried to remove the potential for human error by creating “closed-loop systems” that directly connect the devices that track blood sugar and administer insulin. However, these approaches involve mechanical sensors and pumps, with needle-tipped catheters that have to be stuck under the skin and replaced every few days.

“Injecting the wrong amount of medication can lead to significant complications like blindness and limb amputations, or even more disastrous consequences such as diabetic comas and death,” said co-senior author John Buse, MD, PhD, Director of the UNC Diabetes Care Center.

Instead of inventing another completely man-made system, the smart patch investigators decided to mimic the function of pancreatic cells, which sense increases in blood sugar levels and signal the release of insulin into the bloodstream.

“We constructed artificial vesicles to perform these same functions by using two materials that could easily be found in nature,” said first author Jiching Yu, a PhD student in Dr. Gu’s lab. The first material was hyaluronic acid (HA). The second was 2-nitroimidazole (NI), an organic compound commonly used in diagnostics.

The researchers connected the two to create a new molecule with one end that was hydrophilic and one that was hydrophobic. These molecules self-assembled into artificial vesicles with the hydrophobic ends pointing inward and the hydrophilic ends pointing outward. Into each of these vesicles, the researchers inserted a core of solid insulin and enzymes specially designed to sense glucose.

In lab experiments, when blood glucose levels increased, the excess glucose crowded into the artificial vesicles. The enzymes then converted the glucose into gluconic acid, consuming oxygen all the while. The resulting hypoxia made the hydrophobic NI molecules turn hydrophilic, causing the vesicles to rapidly fall apart and send insulin into the bloodstream.

Once the researchers designed these “intelligent insulin nanoparticles,” they had to figure out a way to administer them to patients with diabetes. Rather than rely on the large needles or catheters that had beleaguered previous approaches, they decided to incorporate these glucose-responsive vesicles into an array of tiny needles.

Dr. Gu created the microneedles using the same hyaluronic acid in the nanoparticles, only in a more rigid form to pierce the skin, and arrayed on a thin silicon strip. When this patch is placed on the skin, the microneedles penetrate and tap into the blood flowing through the capillaries just below the surface.

To test this delivery method, the researchers experimented on mice with chemically-induced type 1 diabetes. Blood glucose levels in control mice given a standard injection of insulin dropped down to normal but then quickly climbed back into the hyperglycemic range. In contrast, when the researchers treated another set of mice with the microneedle-array patch, blood glucose levels were not only under control within 30 minutes but were sustained at normal levels for several hours.

In addition, the researchers found that they could “tune” the patch to alter blood glucose levels within a certain range by varying the dose of enzyme contained within each of the microneedles. They also found that the patch did not pose the hazards that poorly-timed insulin injections can have.

“The hard part of diabetes care is not the insulin shots, or the blood sugar checks, or the diet, but the fact that you have to do them all several times a day every day for the rest of your life,” said Dr. Buse, who is also Director of the North Carolina Translational and Clinical Sciences (NC TraCS) Institute in Chapel Hill, NC, and past president of the American Diabetes Association. “If we can get these patches to work in people, it will be a game changer.”

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