静电纺纤维滴鼻液实现脑室内给药  

Swimming short fibrous nasal drops achieving intraventricularadministration

作　　者：王娟 王秋云 符一飞 卢敏 陈亮 刘志恒 付晓晗 杜习羽 于布为 陆菡 崔文国 Juan Wang;Qiuyun Wang;Yifei Fu;Min Lu;Liang Chen;Zhiheng Liu;Xiaohan Fu;Xiyu Du;Buwei Yu;Han Lu;Wenguo Cui(Department of Orthopaedics,Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases,Shanghai Institute of Traumatology and Orthopaedics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Department of Anesthesiology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Department of Anesthesiology,Shenzhen Second People’s Hospital,The First Affiliated Hospital of Shenzhen University,Shenzhen 518035,China;Department of Anesthesiology,Huadong Hospital Affiliated to Fudan University,Shanghai 200040,China)

机构地区：[1]Department of Orthopaedics,Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases,Shanghai Institute of Traumatology and Orthopaedics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [2]Department of Anesthesiology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [3]Department of Anesthesiology,Shenzhen Second People’s Hospital,The First Affiliated Hospital of Shenzhen University,Shenzhen 518035,China [4]Department of Anesthesiology,Huadong Hospital Affiliated to Fudan University,Shanghai 200040,China

出　　处：《Science Bulletin》2024年第9期1249-1262,共14页科学通报（英文版）

基　　金：supported by the National Key Research and Development Program of China (2020YFA0908200);the National Natural Science Foundation of China (82271204, 81771138, and32000937);the Shanghai Municipal Health Commission(20204Y0354);Sanming Project of Medicine in Shenzhen(SZSM202211007)。

摘　　要：Adequate drug delivery across the blood–brain barrier(BBB) is a critical factor in treating central nervous system(CNS) disorders. Inspired by swimming fish and the microstructure of the nasal cavity, this study is the first to develop swimming short fibrous nasal drops that can directly target the nasal mucosa and swim in the nasal cavity, which can effectively deliver drugs to the brain. Briefly, swimming short fibrous nasal drops with charged controlled drug release were fabricated by electrospinning, homogenization,the π-π conjugation between indole group of fibers, the benzene ring of leucine-rich repeat kinase 2(LRRK2) inhibitor along with charge-dipole interaction between positively charged poly-lysine(PLL)and negatively charged surface of fibers;this enabled these fibers to stick to nasal mucosa, prolonged the residence time on mucosa, and prevented rapid mucociliary clearance. In vitro, swimming short fibrous nasal drops were biocompatible and inhibited microglial activation by releasing an LRRK2 inhibitor. In vivo, luciferase-labelled swimming short fibrous nasal drops delivered an LRRK2 inhibitor to the brain through the nasal mucosa, alleviating cognitive dysfunction caused by sepsis-associated encephalopathy by inhibiting microglial inflammation and improving synaptic plasticity. Thus, swimming short fibrous nasal drops is a promising strategy for the treatment of CNS diseases.

关 键 词：Nasal drops Electrospun short fibers Nasal mucosa Intraventricular administration Brain diseases 

分 类 号：R943[医药卫生—药剂学]