BACE_(1)酶响应型脑神经元靶向递药系统的构建及其安全性考察

Construction of A BACE_(1) Enzyme-responsive Brain Neuron-targeted Drug Delivery System and Its Safety Investigation

制备了BACE_(1)酶响应型载体嵌段聚合物MPEG-BA linker-PZLL。以槲皮素作为载药亦可发挥其抗氧化的作用来缓解阿尔茨海默症患者脑内的氧化应激状态,与纳米递药系统结合后能更好地提高其释药率,并可通过响应肽对于BACE_(1)酶消耗来减少Aβ肽的形成。运用薄膜分散法来制备载槲皮素的BACE_(1)酶敏感靶向纳米递药系统。检测了聚合物载体的核磁以及粒径、形态、电位等指标,呈现出典型的球状纳米结构,判断该系统已成功构建;并初步评价了Quc@MBP NPs的体外释放和体外安全性,在小鼠脑微血管内皮细胞和大鼠神经元细胞上显示了较好的安全性,验证了其作为抗AD药物递送载体的潜力。该递药系统设计简单,质量可控,具有良好的体外形貌和安全性,为抗阿尔茨海默病的纳米载体的设计提供了新思路。

A BACE_1-responsive carrier block polymer,MPEG-BA linker-PZLL,was prepared,and Quercetin,as a drug carrier,can also play an antioxidant role to alleviate the oxidative stress in the brain of Alzheimer's patients,and when combined with the nano-delivery system,it can enhance the release rate of Quercetin and reduce the formation of Aβ peptide by depleting the responsive peptide to the BACE_(1) enzyme.A film dispersion method was used to prepare Quercetin-loaded BACE_(1) enzyme-sensitive targeted nanodelivery systems.NMR,as well as the particle size,morphology and potential of the polymer carriers,were examined,which showed typical spherical nanostructures,and it was judged that the system had been successfully constructed.The in vitro release and in vitro safety of the Quc@MBP NPs were also preliminarily evaluated,and they showed a good safety profile on the mouse brain microvascular endothelial cells and rat neuronal cells,which verified their potentials as the delivery carriers of the anti-AD drugs.The drug delivery system was simple in design,controllable in quality,had good in vitro morphology and safety,and provided a new idea for the design of anti-Alzheimer's disease nanocarriers.