Researchers have succeeded in developing a biochemical body patch containing dissolving micro-needles to treat type 2 diabetes patients. The biochemical composition of the inorganic compounds in the patch reacts to blood chemistry in order to control blood sugar levels automatically. In an experiment on mice, the researchers showed that the chemicals in the blood regulate blood sugar for days.
![Conceptual illustration of a patch carrying microneedles for the treatment of type 2 diabetes patients. [Courtesy: Chen lab, NIBIB]](https://www.hayadan.org.il/images/content3/2018/02/Fig-1-patch-part.jpg.webp)
"This research approach could be a way to take advantage of the fact that patients with type 2 diabetes can still produce some insulin," said the lead researcher. "A solution of a body patch containing loose micro-needles is also less complicated and painful than the routine treatments that require frequent blood tests."
Insulin is a hormone produced in the pancreas and secreted into the bloodstream in order to regulate the concentration of glucose in the blood in response to food absorption. The insulin itself is required by the body in order to introduce the glucose from the bloodstream into the cells, where it is converted into energy available for the body's actions, or it is accumulated for future use. In type 1 diabetes, which is usually diagnosed during childhood and adolescence, the body does not produce insulin at all. Type 2 diabetes, which can develop at any age, although it is more common in adults, gradually reduces the body's ability to produce or effectively use the insulin that is available. If it is not treated properly, diabetes can cause cardiac and nerve damage in the body, along with negative and aggravating consequences for the activity of the eyes, legs, kidneys and heart. The global scope of all types of diabetes is approximately 285 million patients, with 90% of them suffering from type 2 diabetes. Many of these patients are required to undergo insulin injections under the skin in amounts that correspond to their individual condition. In half of the patients the insulin treatment is not successful.
The researchers tested an alternative healing approach to regulate blood sugar levels in type 2 diabetes patients with the help of a sticker that is stuck on the skin and works without any pain. The researchers, as part of an article published a long time ago in the scientific journal Nature Communications., applied the treatment in question to mice, in order to demonstrate the capabilities of the treatment and its effectiveness.
The basis of the innovative patch is a substance called alginate (alginate, a salt of alginic acid), a natural rubber-like substance obtained through an extraction process from brown algae. The extract is mixed together with medicinal substances and inserted into micro-needles creating a patch. "Alginate is a flexible material - it is soft, but not too soft," explains the researcher. "It needs to be adapted as a material that can be inserted into the skin layer (dermis), and although it is not commonly used as a filler for needles, it seems to function properly in our case."
The researchers combined the alginate with the composition of biochemical particles that encourage the self-production of insulin in the body when it is needed, and stop encouraging its secretion when the normal blood sugar concentration is reached. The reactive transport system in the patch can supply the body's requirements for days, instead of using the entire amount at once. "Diabetes is a very serious disease, and it affects many people," explains the lead researcher. "All researchers in this field are looking for a drug for long-term use."
The composition of the researchers combines two drugs: exendin-4 and glucose oxidase, in one patch. Each of the two drugs reacts with the blood components and encourages the secretion of insulin. Each of the drug molecules is attached to a particle of a phosphorous mineral, this in order to stabilize it until the time of its use. The increase in the acidity of the blood, which occurs when the concentration of sugar in the blood increases, causes the chemical bond between the mineral particle and the drug to weaken and then it is released for its activity. The drug exendin-4 is similar in its composition to the compound that the body itself secretes from the intestine in response to food absorption. Although this drug is slightly weaker than the natural molecule, the research team specifically chose it because it does not break down in the bloodstream until after about an hour or more, so its activity is relatively long-term. However, it can cause nausea when too much of it is absorbed into the blood. In order to control the absorption rate of the drug, the researchers attached it to a mineral particle of calcium phosphate that stabilizes it until another chemical reaction occurs. This other chemical reaction occurs following the presence of the second drug in the patch, glucose oxidase, which is also stabilized by a mineral particle of copper phosphate. The researcher explains that when the blood sugar levels exceed a certain value, they initiate a reaction of copper phosphorylation with glucose oxidase which causes a moderate increase in the level of acidity, a situation that causes the calcium phosphorylation to release part of the drug exendin-4. The increase in sugar levels initiates the release of exendin-4; At this moment, the drug causes the secretion of insulin while lowering the blood sugar levels, which slows down and therefore stops the release of exendin-4. "Thanks to this mechanism, we call this activity reactive release, or smart," says the researcher. "Most existing approaches involve releasing at a constant rate. Our approach creates a wave of rapid release when needed and then slows down or even stops the release when blood sugar levels stabilize at the normal threshold."
The researchers demonstrated the effectiveness of the patch, measuring 3 square centimeters, which contains a sufficient amount of medicine to control blood sugar levels in mice for about a week. In order for the approach to progress and become applicable for patients with type 2 diabetes, the team will have to conduct experiments in which larger animals will be treated with the patch containing larger amounts, in appropriate proportion to the animal's weight. In addition to adjusting its size, the patch will also need to fit human skin, presumably using longer needle tips. "We will have to increase the size of the sticker and adjust the length, shape and structure of the needles," says the researcher. "In addition, the sticker will have to be suitable for everyday life, for example when showering or when exposed to sweat."
The researchers are encouraged by the success of their experiments, and by other research reports describing consistent progress made by researchers in the field of microneedle-carrying patches. For example, researchers have completed preliminary studies in humans using patch devices that carry microneedles containing insulin, a solution that could be beneficial for both type 1 and type 2 diabetes patients.
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