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.
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. 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, 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.
Researchers 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. Researchers puts two drug compounds -- exendin-4 and glucose oxidase -- into one patch. The two compounds react with the blood chemistry to trigger insulin secretion. Each is matched with a phosphate mineral particle, which stabilizes the compound until it is needed. Acidity that occurs when sugar concentrations rise weakens the bond with the drug being held by one, but not the other mineral.
Exendin-4 is similar in genetic makeup to a molecule the body produces and secretes in the intestine in response to food intake. Though it is somewhat weaker than the naturally occurring molecule, the team chose exendin-4 for its application because exendin-4 does not degrade in the bloodstream for an hour or more, so can have long-lasting effect after being released. However, it can induce nausea when too much is absorbed. To control how quickly it is absorbed, the researchers combined exendin-4 with mineral particles of calcium phosphate, which stabilize it until another chemical reaction occurs. That chemical reaction is caused by the second drug compound in the patch -- glucose oxidase -- that is held in its mineral buffer of copper phosphate.
When blood sugar is elevated beyond a precise point, it triggers a reaction with copper phosphate and glucose oxidase to produce slight acidity, which causes calcium phosphate to release some exendin-4. Rising glucose levels trigger the release of exendin-4; but exendin-4 then gets insulin flowing to reduce the glucose level, which slows down and stops release of exendin-4. The researchers demonstrated that a patch about half an inch square contained sufficient drug to control blood sugar levels in mice for a week.
For the approach to advance as an application that people with type-2 diabetes can use, the team will need to perform tests to treat larger animals with a patch that contains proportionately more therapeutic compound. In addition to its size, the patch would need to be altered for application on human skin, likely requiring longer needles.
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