Smart insulin patch could replace injections for diabetes

Painful insulin injections could become a thing of the past thanks to researchers at the University of North Carolina (UNC) and North Carolina State University (NC State). The solution is a smart insulin patch that can detect increases in blood sugar levels and secrete doses of insulin into the bloodstream whenever needed.

The patch – a thin square no bigger than a penny – is covered with more than 100 tiny needles, each about the size of an eyelash. The microneedles are packed with microscopic storage units for insulin and glucose-sensing enzymes that rapidly release their cargo when blood sugar levels get too high.

The study found that the painless patch could lower blood glucose in a mouse model of Type 1 diabetes for up to nine hours. More pre-clinical tests and subsequent clinical trials in humans will be required before the patch can be administered to patients, but the approach shows great promise.

“We have designed a patch for diabetes that works fast, is easy to use, and is made from nontoxic, biocompatible materials,” says co-senior author Zhen Gu, Ph.D., a professor in the Joint UNC/NC State Department of Biomedical Engineering.

Researchers have tried to remove the potential for human error in insulin therapy by creating closed-loop systems that directly connect 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.

Gu and his colleagues chose to emulate the body’s natural insulin generators, beta cells. These cells make and store insulin in tiny sacs called vesicles. They also behave like alarm call centers, sensing increases in blood sugar levels and signaling 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,” says Jiching Yu, a Ph.D. student in Gu’s lab. The first material was hyaluronic acid, a natural substance that is an ingredient of many cosmetics; and second was 2-nitroimidazole, an organic compound commonly used in diagnostics. The researchers connected the two to create a new molecule with one end that was water-loving, hydrophilic, and one that was water-fearing, hydrophobic. A mixture of these molecules self-assemble into a vesicle, with hydrophobic ends pointing inward and hydrophilic ends pointing outward.

The result was millions of bubble-like structures, each 100x smaller than the width of a human hair. Into each of these vesicles, researchers inserted a core of solid insulin and enzymes designed to sense glucose.

In lab experiments, when blood sugar 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 lack of oxygen or hypoxia made the hydrophobic NI molecules turn hydrophilic, causing the vesicles to rapidly fall apart and send insulin into the bloodstream.

Rather than rely on the large needles or catheters, researchers incorporated the balls of sugar-sensing, insulin-releasing material into an array of tiny needles.

Gu created these microneedles using the hyaluronic acid used in nanoparticles, only in a more rigid form so the needles were stiff enough to pierce the skin. When this patch was placed on the skin, the microneedles penetrated the surface, tapping into the blood flowing through the capillaries just below.

Researchers gave one set of mice a standard injection of insulin and measured the blood glucose levels, which dropped down to normal, but then quickly climbed back into the hyperglycemic range. When the researchers treated another set of mice with the patch, they saw blood glucose levels brought under control within 30 minutes, which stayed that way for several hours.

Researchers found that they could tune the patch to alter blood glucose levels only within a certain range by varying the dose of enzyme contained within each of the microneedles.

“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,” says John Buse, the director of the North Carolina Translational and Clinical Sciences Institute and past president of the American Diabetes Association. “If we can get these patches to work in people, it will be a game changer.”

The researchers’ eventual goal, Gu says, is to develop a smart insulin patch that patients would only have to change every few days.

University of North Carolina
www.unc.edu

North Carolina State University
www.ncsu.edu