A groundbreaking discovery in insulin delivery could one day put an end to the invasive needles that many people with diabetes are forced to use daily.
In a study using mice, pigs and laboratory-grown human skin samples, a team of researchers demonstrated the effectiveness of a topical insulin treatment — which allows the drug to be administered through a cream applied directly to the skin.
This is an achievement for a long time considered impossibledue to the large size of insulin molecules and its strong affinity with water, which prevents its passage through the oily layers of the skin.
The discovery, made by a team led by scientists from Zhejiang University, in China, was presented in a published this Wednesday in the journal Nature.
“The skin-permeable polymer could allow transdermal administration non-invasive use of insulin, relieving diabetic patients from subcutaneous injections and may also facilitate the more comfortable use of other treatments based on proteins and peptides transdermally”, write the authors of the study.
Administration of medications through the skin presents several advantages: can be done easily at home, it’s painless and ensures a controlled and smooth release of the drug in the body, explains .
However, the skin is, by nature, a barrier designed to protect the body from harmful substances. Its outer layer, the stratum corneumis made up of multiple layers of dead cells held together by fats and oils, or lipids.
Os Topical medications bypass the skin’s defenses because they have small molecules that can easily cross the skin barrier and also have the ability to interact with the lipids present.
A insulin, a hormone that regulates glucose levelsdoes not present any of these characteristics. Its molecules are relatively large and have a hydrophilic surface (affinity for water), which makes them chemically incompatible with skin oils. Instead of passing through or sliding between the oils, they end up being repelled.
Despite appearing to be an impenetrable barrier, researchers believed that another property of the skin could help insulin to enter: its acidity. The skin naturally has a pH gradientstarting slightly acidic at the surface and approaching neutrality in the deeper layers.
Scientists then dedicated themselves to developing an administration system that interact with this pH gradientallowing insulin to enter the body.
The result of the research team’s work is based on a polymer called poli[2-(N-óxido-N,N-dimetilamino)etil metacrilato]or OPwhose properties change with variations in pH, and its biocompatibility has already been demonstrated in previous tests.
On the surface of the skin, the OP has a positive chargewhich allows it to adhere to skin lipids. However, at neutral pH, it loses this charge and is freed from lipidsat which point it has already crossed the skin barrier and entered the body.
By binding insulin to OP, forming a compound called OP-Ithe essential hormone take advantage of this “hitchhike” to get through your skin. Sounds promising in theory, right? In practice, the results are even more encouraging.
In human skin models, as well as in diabetic mice, OP-I was found to be more effective at transporting insulin through the skin than insulin alone or combined with another polymer, PEG, used as a control and widely used in various pharmaceutical applications.
In rats, treatment normalized blood glucose levels in less than an hour, with a Efficacy comparable to insulin injections. The values remained stable for 12 hours.
The next step was to study the method in diabetic mini pigswhich are biologically more similar to humans than mice. The effects were comparable: the pigs’ blood glucose levels dropped to normal within two hours and remained stable for 12 hours.
Once in the body, the OP-I accumulates in key tissues in glucose regulation, including the liver, adipose tissue and skeletal muscles, where cells absorb the conjugate and release insulin inside. OP-I activates insulin receptors and enhances glucose uptake and metabolism, just like insulin administered by injection.
Perhaps most important is the fact that it more prolonged and sustained than injected insulin, providing a smoother and longer-lasting effect.
The researchers did not detect signs of inflammationwhich suggests that the treatment may present minimal harmful side effects — although more robust clinical trials are needed to confirm this safety in humans.
Still, these results indicate that frequent insulin injections may one day become thing of the past — and that the system may even be effective with other medications.
