An innovative method has been devised to relieve the pain of diabetic patients who had to stab themselves with needles every day. This is because ‘insulin cream’, which can manage blood sugar levels stably for 12 hours by simply applying it to the skin like a cream, was effective in animal testing.
A research team at Zhejiang University in China announced that they had developed a technology to effectively deliver high molecular weight proteins, such as insulin, into the skin by using the difference in natural acidity (pH) between the skin’s surface and interior. The results of this research were published in the latest issue of Nature, the world’s most authoritative scientific journal.
Insulin is an essential medicine that is like a lifeline for patients with type 1 diabetes and some patients with type 2 diabetes. However, because the molecule size of insulin is so large that it cannot pass through the skin barrier, there is a limitation in having to rely on injections or an insulin pump. Because of this, patients have suffered the inconvenience of having to take daily injections or attach an insulin pump to their bodies, risking pain and infection. In particular, young patients suffered considerable physical and mental pain.
To solve this problem, the research team developed a special polymer material called ‘OP (oligo-arginine-based polymer)’. Normally, the skin surface is slightly acidic (pH 5) and the inside of the skin is neutral (pH 7.4). OP has a positive charge (+) on the acidic skin surface and effectively passes through the skin barrier. When it enters the neutral skin, it changes to an uncharged state and is easily absorbed into blood vessels and lymphatic vessels.
The research team created ‘OP-I’ by combining insulin with this OP and completed ‘insulin cream’. The results of animal testing of insulin cream were successful. When this cream was applied to diabetic rats, blood sugar levels dropped to normal levels within one hour, and the effect remained stable for up to 12 hours, comparable to that of injections. This is a far superior result than the control group combining PEG (polyethylene glycol) and insulin, which were previously widely used in drug delivery.
A similar effect was seen in experiments with mini-pigs, which are biologically more similar to humans. Blood sugar normalized within 2 hours after applying the cream and remained stable for 12 hours.
OP-I absorbed into the body accumulated in tissues key to blood sugar control, such as the liver, fat, and skeletal muscle, and released insulin within the cells. This process activated insulin receptors and promoted glucose metabolism like existing injections, but showed a more gradual and lasting effect than injections. In addition, no serious side effects such as inflammatory reactions have been found in animal tests to date, so it has received a positive evaluation in terms of safety.
In addition, the researchers said that they expect that the OP conjugation technology developed this time can be a new platform for delivering not only insulin but also other macromolecular drugs such as peptides, proteins, and nucleic acids through the skin. In their paper, the research team stated, “OP conjugation technology is a versatile transdermal drug delivery technology that can be applied to a wide range of therapeutic fields,” and added, “It is worth confirming its potential through additional research in the future.”