A polymer for needle-free insulin delivery

A new polymer reported in Nature may mark a turning point for needle-free insulin delivery. Researchers at Zhejiang University have developed a charge-shifting polyzwitterion that can carry insulin through intact skin and into the bloodstream, producing robust glucose-lowering effects in diabetic mice and miniature pigs (Nature 2025, DOI: 10.1038/s41586-025-09729-x).According to co-author Youqing Shen, transdermal delivery typically works only for small, hydrophobic molecules with masses under 500 Da. Larger molecules, including peptides, proteins, and virtually all polymers, are blocked by the dense lipid matrix of the stratum corneum, the outermost layer of skin. That the barrier is so effective that cosmetic safety assessments generally exempt polymers larger than 1,000 Da from skin penetration studies, Shen says. The new study challenges that assumption by demonstrating a synthetic polymer, poly[2-(N-oxide-N,N-dimethylamino)ethyl methacrylate], or OP, capable of efficiently crossing the skin and carrying insulin (~5,800 Da) along with it.The polymer works by taking advantage of the skin’s natural shift in acidity from the surface downward. At the stratum corneum, the environment is mildly acidic, which causes some of the surface lipids to lose protons and take on a slight negative charge. OP becomes positively charged under these acidic conditions, so it is electrostatically drawn to the negatively charged lipids. This attraction helps OP latch onto and slip between the oily layers of this barrier, which normally blocks large molecules such as insulin. A few layers deeper, where the pH becomes neutral, OP automatically switches to a zwitterionic, overall neutral state. In this form, it no