Advanced drug vehicle exploitation and the sophisticated synergy mechanism revelation are two great difficulties in combination therapy. Compared with most readily available polymer micelles, some undiscovered complex chemical design principles limit the expanding research of polymer vesicles. Here, polycaprolactone (PCL)-g-Dextran vesicle that dextran brush steric hindrance guide PCL lamellae-aligned growth was synthesized. The effect of the glycometabolism multi-drug vesicle combination treatment and synergism mechanism were investigated on senescence-accelerated mouse prone 8 (SAMP8) mice. The main insulin sensitizer drug could improve the memory ability of mice to a small extent, and the main insulin secretion promoter drug had little beneficial effect. Moreover, the triple anti-insulin resistant drugs of insulin (INS), repaglinide (REP) and metformin hydrochloride (MET) activated the glycometabolism-related bio-signals, and the energy cycle was normalized successfully. The insulin intracellular uptake and utilization efficiency could be the reason for the gap. The upregulation of the brain-derived neurotrophic factor (BDNF) protein confirmed that the crosstalk between the mitochondria and synapse contributes to the nerve repair. This study provided an excellent drug combination vesicle to treat Alzheimer's disease (AD). The discovery of the combination mechanism leads to an improvement in the AD clinical treatment.

中文翻译：

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亲水性阻碍和疏水性生长：一种针对阿尔茨海默病的囊泡糖代谢多药联合疗法

先进的药物载体开发和复杂的协同机制揭示是联合治疗的两大难点。与最容易获得的聚合物胶束相比，一些尚未发现的复杂化学设计原理限制了聚合物囊泡的扩展研究。这里，聚己内酯（PCL）-g-葡聚糖囊泡，葡聚糖刷位阻指导 PCL 薄片对齐生长合成。研究了糖代谢多药囊泡联合治疗的作用和协同机制对加速衰老的小鼠俯卧 8 (SAMP8) 小鼠。主要的胰岛素增敏药物对小鼠的记忆能力有小幅改善作用，主要的胰岛素分泌促进药物几乎没有有益作用。此外，胰岛素（INS）、瑞格列奈（REP）和盐酸二甲双胍（MET）三联抗胰岛素抵抗药物激活了糖代谢相关的生物信号，并成功地使能量循环正常化。胰岛素细胞内摄取和利用效率可能是造成差距的原因。脑源性神经营养因子 (BDNF) 蛋白的上调证实线粒体和突触之间的串扰有助于神经修复。该研究提供了一种极好的药物组合囊泡来治疗阿尔茨海默病 (AD)。联合机制的发现导致了AD临床治疗的改进。