Research Institute for Biomaterials, Tech Institute for Advanced Materials Bioinspired Biomedical Materials & Devices Center, College of Materials Science and Engineering, Jiangsu Collaborative Innovation Center for Advanced Inorganic Function Composites, Suqian Advanced Materials Industry Technology Innovation Center, Nanjing Tech University, Nanjing, China.
Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, Institute for Inheritance-Based Innovation of Chinese Medicine, Marshall Laboratory of Biomedical Engineering, School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China.
Soft Matter. 2024 Nov 13;20(44):8855-8865. doi: 10.1039/d4sm01004c.
Phenylboronic acid (PBA) is a widely exploited glucose-sensitive element for constructing glucose-responsive hydrogels to enable smart insulin delivery. However, its relatively high intrinsic p affects its binding with glucose under physiological conditions and thus limits its application. Herein, we developed a series of boronate-containing PLP-PBA polymers by conjugating glucose-sensitive 3-aminophenylboronic acid (3-PBA) onto the backbone of a metabolite-derived, pH-responsive poly-L-lysine isophthalamide (PLP) polymer with a p value of 4.4 at various substitution degrees. Dual-responsive LME-(PLP-PBA) hydrogels were further synthesized by crosslinking the PLP-PBA polymers with L-lysine methyl ester (LME). The rheological properties and swelling ratio of the hydrogel could be manipulated by the PBA grafting degree and crosslinking ratio. With the increase of pH and glucose concentration, the pore size of the hydrogel enhanced, thus promoting the release of loaded insulin. Under physiological conditions, the hydrogel with optimal formulation could establish acute pH-responsive and glucose-responsive insulin release. The development of this dual-responsive hydrogel suggests a strategy to overcome the high p problem associated with PBA and provide a promising delivery system for smart insulin delivery.
苯硼酸（PBA）是一种广泛应用的葡萄糖敏感元件，用于构建葡萄糖响应水凝胶，以实现智能胰岛素输送。然而，其相对较高的固有 p 值会影响其在生理条件下与葡萄糖的结合，从而限制了其应用。本研究通过将葡萄糖敏感的 3-氨基苯硼酸（3-PBA）连接到具有代谢物衍生、pH 响应的聚-L-赖氨酸异苯甲酰胺（PLP）聚合物主链上来制备一系列含硼酸盐的 PLP-PBA 聚合物，该聚合物的 p 值为 4.4，取代度不同。通过用 L-赖氨酸甲酯（LME）交联 PLP-PBA 聚合物，进一步合成了双响应性 LME-（PLP-PBA）水凝胶。水凝胶的流变性能和溶胀比可以通过 PBA 接枝度和交联比来控制。随着 pH 和葡萄糖浓度的增加，水凝胶的孔径增大，从而促进了负载胰岛素的释放。在生理条件下，具有最佳配方的水凝胶能够建立急性 pH 响应和葡萄糖响应的胰岛素释放。这种双响应性水凝胶的开发为克服 PBA 相关的高 p 值问题提供了一种策略，并为智能胰岛素输送提供了一种有前景的输送系统。
