For many people with diabetes, daily insulin injections are required to manage blood sugar levels, but scientists have invented a new polymer-based gel that allows insulin to be administered through the skin without the use of needles.
The gel, described in a November study published in Nature, normalized blood sugar levels in diabetic mice and pigs within one to two hours of application. Thereafter, the animals’ blood sugar levels remained in the normal range for approximately 12 hours.
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The gel is “mechanically sophisticated,” said Suchetan Pal, associate professor and director of the biomaterials laboratory at the Indian Institute of Technology Bhilai. He was not involved in this study.
However, it is still strictly experimental at this point. To date, the gel has only been tested in mice and pigs, not humans, Pal told Live Science via email. Human skin is variable in thickness, fat content, and pH and can behave differently than animal skin.
How gels slip through the skin’s defenses
The outer layer of human skin, the stratum corneum, is only about 10 to 15 micrometers thick, which is thinner than a human hair. However, the dead cells and fat that make up the layer form a shield that is difficult to penetrate. Some small molecules can pass through this barrier, but large proteins like insulin usually cannot.
The research team overcame this challenge by designing a pH-responsive polymer called OP.
At around pH 5, the surface of the skin is acidic, but the deeper layers of the skin are closer to neutral pH 7. At the surface of the skin, OP polymers are positively charged. This positive charge helps it stick to fatty acids in the skin, much like the two ends of a magnet attract each other.
As the pH gradually increases in deeper layers, the OP polymer changes to a neutral state, allowing it to diffuse through the skin’s fat. This transports insulin chemically bound to the polymer through layers of the skin that it normally cannot penetrate on its own.
Experiments on mouse and pig skin confirmed that OP penetrates all layers of the skin, whereas only insulin remains attached to the surface. The researchers then tested whether applying OP insulin gel to the animals’ skin lowered blood sugar levels.
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In a mouse model of diabetes, application of the gel lowered blood sugar levels to normal range in about an hour and kept them within that range for about 12 hours. However, Pal noted that this effect requires a very high OP insulin dose of 116 units per kilogram of body weight (U/kg), far exceeding the typical insulin dose for humans. This may raise concerns that delivery of insulin through the skin may not be efficient enough.
But notably, the researchers were able to use lower doses of the drug in diabetic minipigs, whose skin closely resembles that of humans. Using a single dose of approximately 7.25 U/kg, the gel restored blood sugar levels to normal levels in pigs. And the research team found that repeated use of this gel did not cause skin irritation or irritation.
Further research required
If the results of these animal studies can be applied to humans, needle-free insulin gel could help patients with a fear or aversion to needles, potentially improving treatment adherence and reducing the burden of diabetes management.
The 12-hour effect suggests that this gel may function as a long-acting insulin that provides “background” blood sugar control, even though patients require fast-acting doses at mealtimes. Pal points out that the gel’s absorption into the bloodstream is slower and more stable than that of an injection, so it cannot immediately reverse high blood sugar levels in an emergency.
The authors are working to adapt OPs to carry GLP-1 agonists such as semaglutide (Ozempic) and other therapeutic proteins, and hope that this polymer approach can be extended beyond insulin delivery. But experts warned that hurdles remained before the gel could be approved for human use.
“This polymer has not shown any side effects in mice or pigs,” study lead author Youqing Shen, a professor at the Department of Chemical and Biological Engineering at Zhejiang University in China, told Live Science via email. “But humans have been using insulin for decades, so long-term toxicity needs to be investigated.”
Shen also said that the dosage of insulin administered through the gel must be carefully controlled, as too much can cause dangerous hypoglycemia. In summary, before skin-based insulin therapy can reach patients, developers will need extensive preclinical safety studies, an investigational new drug (IND) application with the Food and Drug Administration, and human clinical trials.
Although the pig experiments provided a better model of human skin than mice, Pal also cautioned that lower doses of insulin are less effective. This highlights that development is still needed to achieve effective insulin delivery at safe and clinically relevant human doses. The long-term safety of repeated use of the gel is also unknown.
Looking ahead, the team needs to figure out the best formulation and dosage for the gel. Devise ways to scale up manufacturing. Pal said they will then conduct clinical trials. Nevertheless, he finds the idea exciting and believes it could create a path to needle-free diabetes treatment.
This article is for informational purposes only and does not provide medical advice.
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