Needle-free insulin? Scientists invent gel that delivers insulin through the skin in animal studies

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A new polymer gel can deliver insulin through intact skin in animal tests. It could someday offer a path toward needle-free diabetes treatment, some say.

an illustration of sugar molecules in the blood
There may be other options for insulin delivery beyond using needles, an early study suggests. (Image credit: piyaset via Getty Images)

For many people with diabetes, managing their blood sugar levels requires daily insulin shots — but now, scientists have invented a new polymer-based gel that can deliver insulin through the skin without needles.

The gel, described in a November study in the journal Nature, normalized the blood sugar levels of diabetic mice and pigs within one to two hours of application. The animals' blood sugar then stayed in a normal range for approximately 12 hours.

The gel is "mechanistically elegant," said Suchetan Pal, an associate professor and head of the Biomaterials Laboratory at the Indian Institute of Technology Bhilai, who was not involved in the research.

However, for now, it is still strictly experimental. To date, the gel has been tested only on mice and pigs and not on people, Pal told Live Science in an email. Human skin — which is variable in its thickness, fat content and pH — may behave differently than animal skin.

How the gel slips past the skin's defenses

Human skin's outer layer, the stratum corneum, is only about 10 to 15 micrometers thick, thinner than a human hair. But the dead cells and fats that make up the layer form a shield that's tough to penetrate. While some small molecules can cross this barrier, larger proteins, like insulin, normally cannot.

The team behind the study overcame this challenge by engineering a pH-responsive polymer, which they call OP.

At a pH of around 5, the skin's surface is acidic, while deeper layers of the skin are closer to a neutral pH of 7. At the skin's surface, the OP polymer becomes positively charged. This positive charge helps it stick to the fatty acids within the skin, much like opposite ends of a magnet attract each other.

As the pH gradually increases in deeper layers, the OP polymer changes to a neutral state that enables it to diffuse through fats in the skin. Insulin, which is chemically linked to the polymer, is thereby carried through skin layers that it wouldn't normally be able to penetrate on its own.

Lab tests with mouse and pig skin confirmed that OP penetrates all layers of the skin, whereas insulin alone remains stuck on the surface. The researchers then tested whether applying the OP-insulin gel to animals' skin could lower their blood sugar.

In a mouse model of diabetes, applying the gel once lowered their blood glucose to a normal range in about an hour and maintained it within that range for roughly 12 hours. However, Pal noted that this effect required a very high OP-insulin dose of 116 units per kilogram of body weight (U/kg) — far beyond a typical human dose of insulin. ​​This could raise a concern that the insulin delivery through the skin might not be efficient enough.

But notably, the researchers were able to use a lower dose in diabetic miniature pigs, whose skin closely resembles that of humans. Using a single dose around 7.25 U/kg, the gel restored the pigs' blood glucose to normal levels. And using the gel repeatedly caused no skin irritation or inflammation, the team found.

More research needed

If these animal results translate to people, the needle-free insulin gel could potentially help patients with a fear of or aversion to needles, thus helping improve their treatment adherence and easing the burden of diabetes management.

The 12-hour effect suggests the gel could serve as a long-acting insulin to provide "background" blood-sugar control, although patients would still need fast-acting doses at mealtimes. Because the gel's absorption into the bloodstream is slower and steadier than that of an injection, it cannot quickly reverse high blood sugar in an emergency, Pal noted.

The authors hope this polymer approach could extend beyond insulin delivery, as they're working to adapt OP to carry GLP-1 agonists, such as semaglutide (Ozempic), and other therapeutic proteins. However, experts cautioned that hurdles remain before the gel could be approved for human use.

"The polymer hasn't shown any side effects in mice or pigs," said lead study author Youqing Shen, a professor in the School of Chemical and Biological Engineering at Zhejiang University in China, told Live Science in an email. "But humans have used insulin for decades, so we need to investigate long-term toxicity."

Shen also said the insulin dose delivered through the gel must be carefully controlled, since too much can result in dangerously low blood sugar. In sum, developers would need extensive preclinical safety studies, an Investigational New Drug (IND) filing with the Food and Drug Administration, and human clinical trials before a skin-based insulin therapy could reach patients.

While the pig experiments offered a better model of human skin than the mice did, Pal also cautioned that the lower dose of insulin had lower efficacy. This underscores the amount of development still needed to achieve effective insulin delivery at safe and clinically relevant human doses.​​ The long-term safety of using the gel repeatedly is also unknown.

Looking forward, the team will need to figure out the optimal formulation and dosing for the gel; devise a way to scale up its manufacturing; and run clinical trials, Pal said. Nonetheless, he finds the idea exciting and believes it could create an avenue for needle-free diabetes care.

Disclaimer

This article is for informational purposes only and is not meant to offer medical advice.

Article Sources

Source Wei, Q., He, Z., Li, Z. et al. A skin-permeable polymer for non-invasive transdermal insulin delivery. Nature 648, 459–467 (2025). https://doi.org/10.1038/s41586-025-09729-x

Sayan Tribedi
Sayan Tribedi
Live Science Contributor

Sayan Tribedi is a freelance science writer based in Kolkata, India. He holds a bachelor's degree in chemistry from the University of Calcutta and a master's in bioinformatics from Pondicherry University. With research experience in protein-protein interactions, he brings a strong scientific foundation to his writing. Sayan enjoys translating complex scientific ideas into accessible, engaging stories for the general public. His work has appeared in The Hindu and Science Reporter, among other publications.

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