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Science Bulletin 2024年第9期69卷 1249-1262页

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 Department of Orthopaedics Shanghai 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 Anesthesiology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Anesthesiology Shenzhen Second People’s HospitalThe First Afﬁliated Hospital of Shenzhen UniversityShenzhen 518035China Department of Anesthesiology Huadong Hospital Afﬁliated to Fudan UniversityShanghai 200040China

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

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