Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Turin, Italy.
Interuniversity Center for the Promotion of 3Rs Principles in Teaching and Research, Centro 3R, 56122 Pisa, Italy.
Int J Mol Sci. 2023 Feb 8;24(4):3390. doi: 10.3390/ijms24043390.
Intranasal (IN) drug delivery is a non-invasive and effective route for the administration of drugs to the brain at pharmacologically relevant concentrations, bypassing the blood-brain barrier (BBB) and minimizing adverse side effects. IN drug delivery can be particularly promising for the treatment of neurodegenerative diseases. The drug delivery mechanism involves the initial drug penetration through the nasal epithelial barrier, followed by drug diffusion in the perivascular or perineural spaces along the olfactory or trigeminal nerves, and final extracellular diffusion throughout the brain. A part of the drug may be lost by drainage through the lymphatic system, while a part may even enter the systemic circulation and reach the brain by crossing the BBB. Alternatively, drugs can be directly transported to the brain by axons of the olfactory nerve. To improve the effectiveness of drug delivery to the brain by the IN route, various types of nanocarriers and hydrogels and their combinations have been proposed. This review paper analyzes the main biomaterials-based strategies to enhance IN drug delivery to the brain, outlining unsolved challenges and proposing ways to address them.
鼻腔（IN）给药是一种非侵入性且有效的途径，可以将药物以药理相关浓度递送到大脑，绕过血脑屏障（BBB）并最小化不良反应。IN 给药在治疗神经退行性疾病方面特别有前途。药物输送机制包括初始药物穿透鼻上皮屏障，然后沿着嗅神经或三叉神经在血管周围或神经周围空间扩散，最后通过细胞外扩散遍及整个大脑。一部分药物可能通过淋巴系统排出而丢失，而一部分药物甚至可能通过穿透 BBB 进入体循环并到达大脑。或者，药物可以通过嗅神经的轴突直接运输到大脑。为了提高 IN 途径向大脑输送药物的效果，已经提出了各种类型的纳米载体和水凝胶及其组合。本文分析了增强 IN 向大脑递药的主要基于生物材料的策略，概述了未解决的挑战并提出了解决方法。
