Science Highlights

NIH animal study shows dissolvable microneedles trigger body’s own insulin response

For millions of people with type 2 diabetes, ongoing vigilance over the amount of sugar, or glucose, in their blood is the key to health. A finger prick before mealtimes and maybe an insulin injection is an uncomfortable but necessary routine.

Concept illustration of microneedle device for type 2 diabetes treatment. Chen lab, NIBIB. Researchers with NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB) have devised an innovative biochemical formula of mineralized compounds that interacts in the bloodstream to regulate blood sugar for days at a time. In a proof-of-concept study performed with mice, the researchers showed that the biochemically formulated patch of dissolvable microneedles can respond to blood chemistry to manage glucose automatically. Researchers with NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB) have devised an innovative biochemical formula of mineralized compounds that interacts in the bloodstream to regulate blood sugar for days at a time. In a proof-of-concept study performed with mice, the researchers showed that the biochemically formulated patch of dissolvable microneedles can respond to blood chemistry to manage glucose automatically.

“This experimental approach could be a way to take advantage of the fact that persons with type 2 diabetes can still produce some insulin,” said Richard Leapman, Ph.D., NIBIB scientific director. “A weekly microneedle patch application would also be less complicated and painful than routines that require frequent blood testing.”

Insulin is a hormone made in the pancreas and secreted into the bloodstream to regulate glucose in response to food intake. It is needed to move glucose from the bloodstream into cells where the sugar can be converted to energy or stored. In type 1 diabetes, usually diagnosed in children and young adults, the body does not make insulin at all. Type 2 diabetes, which can be diagnosed at any age but more commonly as an adult, progressively lessens the body’s ability to make or use insulin. Untreated, diabetes can result in both vascular and nerve damage throughout the body, with debilitating impacts on the eyes, feet, kidneys, and heart.

Global incidence of all types of diabetes is about 285 million people, of which 90 percent have type 2 diabetes. Many require insulin therapy that is usually given by injection just under the skin in amounts that are calculated according to the deficit in naturally generated insulin in the blood. Insulin therapy is not managed well in half of all cases. NIBIB researchers led by Xiaoyuan (Shawn) Chen, senior investigator in the Laboratory of Molecular Imaging and Nanomedicine, are working on an alternate therapy approach to regulate blood sugar levels in type 2 diabetes using a painless skin patch. In a Nov. 24, 2017, study published online in Nature Communications, the team applied the treatment to mice to demonstrate its potential effectiveness. The base of the experimental patch is material called alginate, a gum-like natural substance extracted from brown algae. It is mixed with therapeutic agents and poured into a microneedle form to make the patch. “Alginate is a pliable material—it is soft, but not too soft,” Chen said. “It has to be able to poke the dermis, and while not a commonly used material for needles, it seems to work pretty well in this case.” Chen’s team infused the alginate with a formula of biochemical particles that stimulates the body’s own insulin production when needed and curtails that stimulation when normal blood sugar concentration is reached. The responsive delivery system of the patch can meet the body’s need for days instead of being used up all at once. “Diabetes is a very serious disease and affects a lot of people,” Chen said, explaining that his group is part of a crowded field of drug research and developers with competing ideas. “Everybody is looking for a long-acting formula.” Illustration to represent glucose-responsive exendin-4 delivery with a microneedle patch. At left, relatively lower glucose levels (turquoise) in blood induce a mild chemical reaction with the compounds in the patch, which is not sufficient to release exendin-4. At right, when blood glucose concentration rises, acidity in blood triggers rapid release of exendin-4 (pink) for blood glucose regulation. The result is a smart, long-acting, and on-demand exendin-4 release. Chen lab, NIBIB.