A skin-permeable polymer for non-invasive insulin delivery

Insulin Cream

Do you live with diabetes and inject insulin daily, or know someone who does? Early animal studies suggest we might someday decrease needle use by delivering insulin with a topical cream.

Introduction

One in nine adults worldwide has diabetes. If you have type 1 diabetes, you need insulin daily to stabilize your blood glucose levels. This means giving yourself insulin shots every day for the rest of your life. Many people adjust to this routine, but others never fully get over their fear of needles. This can make injections stressful and lead to missed doses, delayed injections, or taking less insulin than prescribed.

So what if patients can self-administer it differently? Like using a simple skin cream instead of a needle? That’s the idea behind a new Nature study, “A skin-permeable polymer for non-invasive transdermal insulin delivery.”

Getting a drug through the skin is like passing through airport security with multiple checkpoints. Each layer of skin has a slightly different pH, structure, and stiffness. Some small drug molecules can pass through the skin more easily, like travelers with a TSA Precheck. But insulin is a large protein that cannot get a fast-track pass. In this study, the authors leverage the skin’s natural pH gradient to deliver insulin using a polymer called OP.

OP- the skin-permeable polymer

At the skin surface, opposites attract. The outer layer of skin is slightly acidic, and OP carries a net positive charge there, so it sticks to the fatty barrier. As it diffuses inward and the pH approaches neutral, OP’s charge shifts, making it less sticky and more 'slippery'. This allows OP to continue moving through the deeper layers and enter the bloodstream.

Bonus points for OP since it can not only penetrate the skin but also deliver drugs like insulin. In a diabetic mouse model, a single topical dose of OP-insulin (OP-I) lowered blood glucose levels within about 2 hours. Topical OP-I even maintained normal blood glucose levels for about 12 hours - nearly three times longer than a standard injected insulin in that model. A similar effect was seen in a diabetic minipig model, demonstrating the translatability of OP-I technology in larger animals.

Conclusions - What does this mean for diabetic patients?

This preclinical study demonstrates promising results for topically applied OP-I in lowering blood glucose levels in mice. OP-I represents an important proof of concept for non-invasive delivery of protein drugs. Like all preclinical studies, OP-I will still need to be tested in human clinical trials to determine whether it is safe and effective for patients with diabetes. However, this line of research suggests that some people with diabetes might need fewer injections than they currently do. What excites me even more is the versatility of this platform: similar polymers might one day help deliver protein-based medicines and vaccines without needles.

References

1) Wei, Q. et al. A skin-permeable polymer for non-invasive transdermal insulin delivery. Nature 1–9 (2025) doi:10.1038/s41586-025-09729-x.