重编程
病因学
疾病
病变
神经科学
医学
神经元
病理
生物
细胞
生物化学
作者
Wenqin Yang,Yulong Shi,Yiwei Zhang,Yating Yang,Yufan Du,Zixiao Yang,Xiaorong Wang,Ting Lei,Yanyan Xu,Yongke Chen,Fan Tong,Yazhen Wang,Qianqian Huang,Chuan Hu,Huile Gao
出处
期刊:ACS Nano
[American Chemical Society]
日期:2024-10-16
标识
DOI:10.1021/acsnano.4c09449
摘要
The unsatisfactory treatment outcome of Alzheimer's disease (AD) can be attributed to two primary factors, the intricate pathogenic mechanisms leading to restricted treatment effectiveness against single targets and the hindered drug accumulation in brain due to blood–brain barrier obstruction. Therefore, we developed a carrier-free nanomodulator (NanoDS) through the self-assembly of donepezil and simvastatin for direct nose-to-brain delivery. This approach facilitated a rapid and efficient traversal through the nasal epithelial barrier, enabling subsequent drug release and achieving multiple therapeutic effects. Among them, donepezil effectively ameliorated the symptoms of AD and restored synaptic plasticity. Simvastatin exerted a neurotrophic effect and facilitated the clearance of amyloid-β aggregation. At the same time, NanoDS demonstrated effective anti-inflammatory and antioxidative stress effects. This therapy for AD is approached from both symptomatic and etiological perspectives. In the treatment of FAD4T transgenic mice, it highly improved spatial memory impairment and cognitive deficits while restoring the homeostasis of brain microenvironment. Collectively, our study presented a paradigm for both achieving efficient brain delivery and offering pleiotropic therapies for AD.
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