Metformin-based internally charged nanoparticles for oral insulin delivery with injection-matched efficacy

作者：Songli Zhou, Zhaoyi Chen, Xia Li, Feifan Yue, Lixin Ma, Shuai Zhao, Fei Wang, Jingwen Luo · 发表于：Materials & Design · 年份：2025 · DOI：10.1016/j.matdes.2025.114484 · 被引用次数：4 · 研究领域：Advanced Drug Delivery Systems、Nanoparticle-Based Drug Delivery、Drug Solubulity and Delivery Systems

Oral insulin (INS) has been proven to be the best choice for treating diabetes while reducing side effects and improving patient compliance. However, the implementation of oral INS administration has been hindered by the challenges of rapid degradation, poor stability, and low permeability in the gastrointestinal tract. Here, we designed and synthesized a new amphiphilic triblock copolymer of polyethylene glycol-tridecanedioic acid-metformin (PEG-C 13 -ME) to construct novel oral nanoparticles (NPs) with the function of INS protection and intestinal transport. Metformin imparts a positive charge to the hydrophobic core of nanoparticles, enabling effective encapsulation of insulin and significantly reducing its susceptibility to degradation. The NPs were prepared using the thin-film hydration method. Fourier-transform infrared spectroscopy confirmed the successful incorporation of INS into the NPs. Cytotoxicity assays revealed that both the NPs and INS-loaded nanoparticles (INS-NPs) exhibited low toxicity and good biocompatibility. Confocal laser scanning microscopy and flow cytometry confirmed that INS-NPs enhanced cellular uptake. Additionally, a streptozotocin-induced diabetic mouse model was established, and INS-NPs effectively reduced blood glucose levels in diabetic mice. These findings indicate that our NPs possess excellent stability, low toxicity, and high efficiency in INS delivery, making them a promising oral delivery vehicle for various macromolecular drugs.