近日，浙江大学教授申有青及其课题组揭示了用于非侵入性经皮胰岛素输送的皮肤渗透性聚合物。这一研究成果于2025年11月19日发表在国际顶尖学术期刊《自然》上。

本研究表明，快速透肤性多两性离子聚[2-（N-氧化物-N， N-二甲氨基）甲基丙烯酸乙酯]（OP）能有效渗透角质层、活表皮和真皮层进入循环。OP被质子化为阳离子，因此在酸性皮脂和含有脂肪酸的细胞旁角质层脂质中富集，随后通过角质层间脂质层扩散。角质层下，在正常生理pH下，OP变成中性多两性离子，在细胞膜上“跳跃”，使其能够有效地通过表皮和真皮迁移，最终进入真皮淋巴管和体循环。

结果，OP缀合胰岛素有效地通过皮肤渗透到血液循环中；经皮给药OP结合胰岛素，剂量为116 U kg^-1注入1型糖尿病小鼠体内，迅速将其血糖水平降至正常范围，经皮剂量为29 U kg^-1使糖尿病小型猪的血糖水平正常化。因此，皮肤渗透性聚合物可以实现胰岛素的非侵入性透皮给药，减轻糖尿病患者的皮下注射，并可能通过透皮给药促进其他基于蛋白质和肽的治疗方法的患者友好主题。

据了解，无创皮肤渗透被广泛应用于小分子药物(小于500a)具有适当的疏水性。然而，长期以来，由于皮肤结构造成的强大屏障，它一直被认为对大分子——特别是聚合物、蛋白质和肽——是不可行的。

附：英文原文

Title: A skin-permeable polymer for non-invasive transdermal insulin delivery

Author: Wei, Qiuyu, He, Zhi, Li, Zifan, Zhou, Zhuxian, Piao, Ying, Huang, Jianxiang, Geng, Yu, Zhang, Runnan, Fu, Yaqi, Ye, Jiayi, Yuan, Yue, Zhu, Haoru, Zeng, Jiaheng, Zhang, Yan, Zhou, Quan, Xu, Mingyu, Shao, Shiqun, Tang, Jianbin, Xiang, Jiajia, Chen, Rongjun, Zhou, Ruhong, Shen, Youqing

Issue&Volume: 2025-11-19

Abstract: Non-invasive skin permeation is widely used for convenient transdermal delivery of small-molecule therapeutics (less than 500Da) with appropriate hydrophobicities1. However, it has long been deemed infeasible for large molecules—particularly polymers, proteins and peptides2,3—due to the formidable barrier posed by the skin structure. Here we show that the fast skin-permeable polyzwitterion poly[2-(N-oxide-N,N-dimethylamino)ethyl methacrylate] (OP) can efficiently penetrate the stratum corneum, viable epidermis and dermis into circulation. OP is protonated to be cationic and is therefore enriched in the acidic sebum and paracellular stratum corneum lipids containing fatty acids, and subsequently diffuses through the intercorneocyte lipid lamella. Beneath the stratum corneum, at the normal physiological pH, OP becomes a neutral polyzwitterion, ‘hopping’ on cell membranes, enabling its efficient migration through the epidermis and dermis and ultimately entering dermal lymphatic vessels and systemic circulation. As a result, OP-conjugated insulin efficiently permeates through the skin into the blood circulation; transdermal administration of OP-conjugated insulin at a dose of 116Ukg1 into mice with type 1 diabetes quickly lowers their blood glucose levels to the normal range, and a transdermal dose of 29Ukg1 normalizes the blood glucose levels of diabetic minipigs. Thus, the skin-permeable polymer may enable non-invasive transdermal delivery of insulin, relieving patients with diabetes from subcutaneous injections and potentially facilitating patient-friendly use of other protein- and peptide-based therapeutics through transdermal delivery.

DOI: 10.1038/s41586-025-09729-x

Source: https://www.nature.com/articles/s41586-025-09729-x