Smart patch for diabetes automatically lowers blood sugar levels

Scientists demonstrated a new “smart cell patch” that quickly reduced and then maintained blood glucose at a stabilized level for more than 10 hours in diabetic mice, according to a study published online March 1, 2016 in Advanced Materials.

The minimally-invasive patch is filled with natural beta cells that sense the body’s glucose signals and respond by secreting doses of insulin on demand to control blood glucose levels, with no risk of inducing hypoglycemia. The patch could greatly simplify how millions of people with type 1 and advanced type 2 diabetes manage the challenging job of maintaining glycemic control, the researchers noted.

For decades, researchers have investigated the transplantation of insulin-producing cells as way to control glucose in people with diabetes. The first successful transplant of human beta cells was performed in 1990, and since then hundreds of patients with diabetes have undergone the procedure. Yet, only a fraction of treated patients achieved normal blood glucose levels. Most transplants are rejected, and many of the medications used to suppress the immune system wind up interfering with the activity of beta cells and insulin.

More recently, researchers have attempted to encapsulate beta cells into biocompatible polymeric cells that could be implanted in the body. In this study, scientists at the University of North Carolina at Chapel Hill in Chapel Hill, NC, and North Carolina State University in Raleigh, NC, enhanced the design their previous innovation—the painless “smart insulin patch.” The patch requires no implantation because it’s applied to the skin, and it’s also outside the immune system.

“This study provides a potential solution for the tough problem of rejection, which has long plagued studies on pancreatic cell transplants for diabetes,” said senior author Zhen Gu, PhD, Assistant Professor in the joint UNC/NC State Department of Biomedical Engineering. “Plus, it demonstrates that we can build a bridge between the physiological signals within the body and these therapeutic cells outside the body to keep glucose levels under control.”

The “smart cell patch,” which is no bigger than a postage stamp, is covered on one side with an array of 400 microneedles—each only 800 μm in length. The microneedles are composed of hyaluronic acid and packed with thousands of pancreatic beta cells and glucose-signal amplifiers. When the patch is applied, the microneedles poke through the skin into capillaries and blood vessels, forming a connection between the internal environment and the external cells of the patch.

During hyperglycemia, the glucose-signal amplifiers—which are made of hypoxia-sensitive materials—respond to the rapid glucose oxidation by quickly releasing encapsulated enzymes. These enzymes diffuse into the externally positioned beta-cell capsules, which accelerates their secretion of insulin into the capillaries and vessels.

In experiments in a mouse model of diabetes, the scientists showed that the patch quickly lowered blood glucose in the mice to normal levels (about 200 mg/dL) within 2 hours, and maintained that level for 6 hours without peaks of hyperglycemia or hypoglycemia.

Next, the researchers sought to verify that the patch could regulate blood glucose without lowering it too much, so they administered a second patch to the mice at 6 hours after the first one. As they had hoped, repeated administration of the patch did not result in excess doses of insulin, and thus did not risk hypoglycemia. Instead, the second patch extended the life of the treatment to 20 hours.    

These results provide a proof of principle for an alternative approach that could be safer and less cumbersome than current insulin treatments, the authors predict. However, further modifications and pre-clinical tests will be needed before the researchers can undertake clinical trials in humans.

“Managing diabetes is tough for patients because they have to think about it 24 hours a day, seven days a week, for the rest of their lives,” said study co-author John Buse, MD, PhD, Professor of Medicine at the UNC School of Medicine and Director of the UNC Diabetes Care Center. “These smart insulin approaches are exciting because they hold the promise of giving patients some time off with regards to their diabetes self-care. It would not be a cure but a desperately needed vacation.”