上海交通大学医学院附属瑞金医院崔文国、陆菡、于布为课题组取得一项新突破。他们的最新研究揭示了游泳短纤维鼻滴剂实现脑室内给药。2024年3月6日出版的《科学通报》杂志发表了这项成果。

跨越血脑屏障给药是治疗中枢神经系统(CNS)疾病的关键因素。本研究受游动鱼类和鼻腔微结构的启发，首次研制出可直接靶向鼻黏膜并在鼻腔内游动的游动短纤维滴鼻液，可有效将药物输送至大脑。

简单地说，通过静电纺丝、均质、纤维吲哚基团之间的π-π共轭、富含亮氨酸的重复激酶2 (LRRK2)抑制剂的苯环，以及带正电荷的聚赖氨酸(PLL)与带负电荷的纤维表面之间的电荷偶极相互作用，制备了具有带电控制释放的游泳短纤维鼻滴剂；这使得这些纤维可以粘附在鼻黏膜上，延长了在粘膜上的停留时间，并阻止了粘膜纤毛的快速清除。

在体外，游泳短纤维滴鼻液具有生物相容性，并通过释放LRRK2抑制剂抑制小胶质细胞的激活。在体内，荧光素酶标记的游泳短纤维滴鼻液通过鼻黏膜将LRRK2抑制剂传递到大脑，通过抑制小胶质细胞炎症和改善突触可塑性，来减轻败血症相关脑病引起的认知功能障碍。因此，游泳短纤维滴鼻液是治疗中枢神经系统疾病的一种很有前景的策略。

附：英文原文

Title: Swimming short fibrous nasal drops achieving intraventricular administration

Author: anonymous

Issue&Volume: 2024/03/06

Abstract: Adequate drug delivery across the blood-brain barrier 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.

DOI: 10.1016/j.scib.2024.03.013

Source: https://www.sciencedirect.com/science/article/abs/pii/S2095927324001579