静电纺纤维滴鼻液实现脑室内给药
Swimming short fibrous nasal drops achieving intraventricularadministration作者机构:Department of OrthopaedicsShanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Department of AnesthesiologyRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Department of AnesthesiologyShenzhen Second People’s HospitalThe First Affiliated Hospital of Shenzhen UniversityShenzhen 518035China Department of AnesthesiologyHuadong Hospital Affiliated to Fudan UniversityShanghai 200040China
出 版 物:《Science Bulletin》 (科学通报(英文版))
年 卷 期:2024年第69卷第9期
页 面:1249-1262页
核心收录:
学科分类:100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学]
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)
主 题:Nasal drops Electrospun short fibers Nasal mucosa Intraventricular administration Brain diseases
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.