Jiang Jing, Xing Yue, Liu Shumeng, Na Yue, Lei Xia, Geng Fang, Zhang Yafeng, Yang Lihong, Zhang Ning
College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.
Heilongjiang Institute for Drug Control (NMPA Key Laboratory for Quality Research and Evaluation of Traditional Chinese Medicine), Harbin, Heilongjiang, China.
J Drug Target. 2025 Jun 9:1-12. doi: 10.1080/1061186X.2025.2514575.
Naringin (4',5,7-trihydroxyflavanone-7-rhamnoglucoside, NG), a potential treatment for Alzheimer's disease (AD), has strong neuroprotective effects but is limited by poor solubility, low bioavailability, and limited brain accumulation. To address these issues, we developed ANG-NG-NPs, a novel NG-loaded poly (ethylene glycol)-poly(ε-caprolactone) copolymers (PEG-PCL) nanoparticle modified with the brain-targeting peptide Angiopep-2 (TFFYGGSRGKRNNFKTEEY, ANG). ANG-NG-NPs exhibited an average size of 126.1 ± 4.50 nm, a zeta potential of -2.97 ± 0.29 mV, 73.43 ± 0.80% encapsulation efficiency (EE), and 24.68 ± 0.45% drug loading capacity (LC). release studies confirmed its sustained-release properties. , ANG-NG-NPs extended NG's circulation time and increased brain uptake. Notably, ANG-NG-NPs restored learning and memory in APP/PS1 mice, improved hippocampal cell health, and reduced hyperphosphorylated tau protein (p-Tau) expression. These findings suggest ANG-NG-NPs as a promising brain-targeting system for treating central nervous system disorders.
柚皮苷（4',5,7-三羟基黄酮-7-鼠李糖葡萄糖苷，NG）是一种治疗阿尔茨海默病（AD）的潜在药物，具有很强的神经保护作用，但受限于其溶解度差、生物利用度低和脑内蓄积有限。为了解决这些问题，我们开发了ANG-NG-NPs，一种用脑靶向肽血管生成素-2（TFFYGGSRGKRNNFKTEEY，ANG）修饰的新型载NG聚（乙二醇）-聚（ε-己内酯）共聚物（PEG-PCL）纳米颗粒。ANG-NG-NPs的平均粒径为126.1±4.50nm，zeta电位为-2.97±0.29mV，包封率（EE）为73.43±0.80%，载药量（LC）为24.68±0.45%。释放研究证实了其缓释特性。此外，ANG-NG-NPs延长了NG的循环时间并增加了脑摄取。值得注意的是，ANG-NG-NPs恢复了APP/PS1小鼠的学习和记忆能力，改善了海马细胞健康状况，并降低了过度磷酸化的tau蛋白（p-Tau）表达。这些发现表明ANG-NG-NPs是一种治疗中枢神经系统疾病的有前景的脑靶向系统。
