Researchers at National Institutes of Health’s National Institute of Biomedical Imaging and Bioengineering (NIBIB) have developed a special patch for Type 2 diabetics that helps to control glucose levels in a novel way. The technology, once fully proven out and optimized, may work for days or even weeks at a time.
The patch is made of alginate, a material produced from algae, that is biocompatible and has the strength necessary to penetrate the skin when formed into needles. As such, the patch has alginate needles protruding from its bottom, but in addition there’s also exendin-4 and glucose oxidase mixed in. The compounds work together to release glucose when necessary, while avoiding doing so when glucose levels are near to normal.
Illustration to represent glucose-responsive exendin-4 delivery with a microneedle patch. On top, 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. On bottom, when blood glucose concentration rises, acidity in blood triggers rapid release of exendin-4 (pink) for blood glucose regulation. Chen lab, NIBIB.
Both exendin-4 and glucose oxidase are paired with phosphate mineral particles to stabilize them within the patch, allowing them to be only active when necessary. Rising acidity levels below the surface of the skin, which happens when glucose levels rise, break down the stabilized compounds to allow them to interact with the body.
The researchers showed that their technology allowed them to control blood sugar levels in laboratory mice for up to a week at a time. Next steps will involve modifying the patch to work with larger animals before trying it out on human subjects.
Some more details according to the NIH:
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.
[Xiaoyuan (Shawn) Chen], senior investigator in the Laboratory of Molecular Imaging and Nanomedicineexplained that 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. “That’s why we call it responsive, or smart, release,” said Chen. “Most current approaches involve constant release. Our approach creates a wave of fast release when needed and then slows or even stops the release when the glucose level is stable.”
Study in Nature Communications: Microneedle-array patches loaded with dual mineralized protein/peptide particles for type 2 diabetes therapy…
Via: NIH…