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鼻内给药绕过血脑屏障,将治疗药物靶向输送至中枢神经系统,以治疗神经退行性疾病。

Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease.

作者信息

Hanson Leah R, Frey William H

机构信息

Alzheimer's Research Center at Regions Hospital, HealthPartners Research Foundation, 640 Jackson Street, St, Paul, MN 55101, USA.

出版信息

BMC Neurosci. 2008 Dec 10;9 Suppl 3(Suppl 3):S5. doi: 10.1186/1471-2202-9-S3-S5.

Abstract

Intranasal delivery provides a practical, non-invasive method of bypassing the blood-brain barrier (BBB) to deliver therapeutic agents to the brain and spinal cord. This technology allows drugs that do not cross the BBB to be delivered to the central nervous system within minutes. It also directly delivers drugs that do cross the BBB to the brain, eliminating the need for systemic administration and its potential side effects. This is possible because of the unique connections that the olfactory and trigeminal nerves provide between the brain and external environment. Intranasal delivery does not necessarily require any modification to therapeutic agents. A wide variety of therapeutics, including both small molecules and macromolecules, can be targeted to the olfactory system and connected memory areas affected by Alzheimer's disease. Using the intranasal delivery system, researchers have reversed neurodegeneration and rescued memory in a transgenic mouse model of Alzheimer's disease. Intranasal insulin-like growth factor-I, deferoxamine, and erythropoietin have been shown to protect the brain against stroke in animal models. Intranasal delivery has been used to target the neuroprotective peptide NAP to the brain to treat neurodegeneration. Intranasal fibroblast growth factor-2 and epidermal growth factor have been shown to stimulate neurogenesis in adult animals. Intranasal insulin improves memory, attention, and functioning in patients with Alzheimer's disease or mild cognitive impairment, and even improves memory and mood in normal adult humans. This new method of delivery can revolutionize the treatment of Alzheimer's disease, stroke, and other brain disorders.

摘要

鼻内给药提供了一种实用的、非侵入性的方法,可绕过血脑屏障(BBB)将治疗药物输送到大脑和脊髓。这项技术能使无法穿过血脑屏障的药物在几分钟内输送到中枢神经系统。它还能将确实能穿过血脑屏障的药物直接输送到大脑,消除了全身给药的必要性及其潜在的副作用。这之所以可行,是因为嗅觉神经和三叉神经在大脑与外部环境之间提供了独特的连接。鼻内给药不一定需要对治疗药物进行任何修饰。包括小分子和大分子在内的多种治疗药物都可以靶向作用于受阿尔茨海默病影响的嗅觉系统和相关记忆区域。利用鼻内给药系统,研究人员在阿尔茨海默病的转基因小鼠模型中逆转了神经退行性变并挽救了记忆。鼻内给予胰岛素样生长因子-I、去铁胺和促红细胞生成素已被证明在动物模型中可保护大脑免受中风影响。鼻内给药已被用于将神经保护肽NAP靶向输送到大脑以治疗神经退行性变。鼻内给予成纤维细胞生长因子-2和表皮生长因子已被证明可刺激成年动物的神经发生。鼻内给予胰岛素可改善阿尔茨海默病或轻度认知障碍患者的记忆、注意力和功能,甚至还能改善正常成年人的记忆和情绪。这种新的给药方法可能会彻底改变阿尔茨海默病、中风和其他脑部疾病的治疗方式。

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