Smart patch to take pain and hassle out of insulin injections

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A smart patch boasting an array of over 100 insulin-carrying microneedles could be an option for diabetics in the future(Credit: Zhen Gu, PhD)

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According to the International Diabetes Federation, 387 million people around the world suffer from diabetes, with this number expected to rise to 592 million by 2035. That adds up to a lot of blood sugar checks, diet watching and insulin shots, but researchers in the US have developed a patch that could revolutionize how the disease is managed. The patch contains of more than 100 microneedles, each automatically secreting insulin into the bloodstream when required.

The thought of over a hundred microneedles replacing a single needle might not sound like an appealing trade, but their tiny size makes them less painful than a standard needle despite their numbers. Each microneedle is about the size of an eyelash, with more than 100 crammed onto a patch no bigger than a penny.

In developing the patch, researchers at the University of North Carolina (UNC) and North Carolina State University (NC State) sought to mimic the body's beta cells, which both produce and store insulin in tiny sacs called vesicles, as well as signalling the release of insulin into the bloodstream when they detect an increase in blood sugar levels.

To create artificial vesicles, the team started with hyaluronic acid (HA), which is a natural substance used in many cosmetics. They then combined HA with 2-nitroimidazole (NI), an organic compound commonly used in diagnostics, to produce a new molecule that was hydrophilic (has an affinity for water) at one end and hydrophobic (repels water) at the other. Similar to the way oil droplets coalesce in water, a mix of these new molecules self-assembled into a vesicle with the hydrophobic ends pointing inwards and the hydrophilic ends pointing outwards.

Into each of these vesicle structures, which were 100 times smaller than the width of a human hair, the researchers inserted a core of solid insulin and glucose-sensing enzymes. Lab experiments showed that in response to a rise in blood sugar levels, excess glucose flooded into the artificial vesicles and was converted into gluconic acid by the enzymes. This process consumed oxygen, the resulting lack of which turned the hydrophobic NI molecules hydrophilic and prompted the vesicles to fall apart and release their insulin payload.

Once they had created these "intelligent insulin nanoparticles," the researchers needed a delivery method, deciding upon incorporating the artificial vesicles into an array of microneedles. These were created using a more rigid form of the same hyaluronic acid that went into the nanoparticles, thereby enabling the microneedles to pierce the skin. These were than placed on a thin silicon strip to form a patch with an array of over 100 microneedles, which are able to penetrate the skin and deliver their payload into the capillaries just below the surface.

In tests, one group of mice with type 1 diabetes was given a standard insulin injection, which caused their blood sugar levels to drop back to normal before quickly climbing back into the hyperglycemic range. However, the blood glucose levels of another group of mice dropped to normal levels within 30 minutes of being treated with the microneedle patch, and stayed that way for several hours. The researchers believe the blood sugar-stabilizing effects of the patch could last even longer in humans, as mice are less sensitive to insulin than we are.

By varying the amount of glucose-sensing enzymes in the vesicles, the researchers also found they were able to tune the patch so it altered blood glucose levels only within a certain range. Additionally, the patch didn't send blood sugar levels plummeting to dangerously low levels, which can be a hazard with administering standard injections too frequently.

"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, PhD, a professor in the Joint UNC/NC State Department of Biomedical Engineering. "The whole system can be personalized to account for a diabetic’s weight and sensitivity to insulin, so we could make the smart patch even smarter."

The team's ultimate goal is to develop a patch that would only need to be changed every few days – which would surely be an attractive proposition for diabetics.

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