Managing diabetes requires regular insulin delivery, but injections remain invasive and burdensome for patients. While transdermal drug delivery works well for small molecules, the skin acts as a strong barrier to large biologics such as insulin. Current strategies to overcome this barrier, including microneedles and ultrasound, often damage the skin and limit long-term use. Now, a new skin-compatible approach has enabled insulin to cross intact skin and control blood glucose levels in animal models, with effects comparable to injections.

Researchers at Zhejiang University (Hangzhou, China) have developed a fast skin-permeable polymer that is designed to move through the skin’s layered structure by responding to natural pH gradients across the epidermis and dermis. The polymer, poly[2-(N-oxide-N,N-dimethylamino)ethyl methacrylate], interacts with the skin without disrupting its architecture. When mixed with insulin, it acts as a carrier, transporting the hormone across the skin barrier and into systemic circulation while preserving insulin’s biological activity.

Unlike invasive enhancement methods, the polymer enables passive penetration through intact skin. Once delivered, insulin accumulates in glucose-regulating tissues such as the liver and skeletal muscle. This mechanism avoids structural damage to skin layers and does not rely on external devices or physical skin disruption. The polymer–insulin combination was tested in diabetic mice and minipigs.

In both models, topical application reduced blood glucose to normal levels within one to two hours, matching the performance of injected insulin, and maintained glucose control for up to 12 hours. Extensive safety testing showed no detectable toxicity in skin cells, blood cells, or major organs, including the liver and kidneys. The polymer achieved skin permeation without altering skin structure, confirming that insulin retained full biological function after transdermal delivery. The findings, published in Nature, suggest a promising noninvasive alternative to insulin injections for diabetes management.

In addition to insulin, the strategy may provide a versatile platform for delivering other therapeutic proteins and peptides through the skin. Further studies are planned to evaluate long-term safety, dose control, and clinical feasibility. If validated in humans, this approach could significantly improve patient comfort and expand the scope of transdermal biologic therapies. According to the researchers, the polymer enables efficient skin permeation while maintaining insulin activity, supporting its potential as a noninvasive platform for delivering biomacromolecules in future therapeutic applications.

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