Drug delivery across the blood-brain barrier
Drug delivery across the blood-brain barrier
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DOI：
10.2174/1567201043334542
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发表时间：
2004-10-04
影响因子：
2.4
通讯作者：
Benson, H. A. E.
中科院分区：
文献类型：
--
作者：
Chen, Y.;Dalwadi, G.;Benson, H. A. E.
大脑受到一种高效的血脑屏障的保护，并与全身循环隔离。这是以相对不透性的内皮细胞为特征的，具有紧密的连接、酶活性和活跃的外排运输系统。因此，血脑屏障被设计成允许选择性地运输对大脑功能至关重要的分子。这给中枢神经系统疾病的治疗带来了相当大的挑战，这些疾病需要治疗水平的药物进入大脑。一些小的亲脂性药物通过血脑屏障扩散--足够好，足以有效。然而，许多潜在有用的药物被排除在外。这篇综述提供了对小分子、多肽和蛋白质靶向大脑的技术的当前研究的洞察。简要回顾了血脑屏障的性质及其转运机制。靶向和改善血脑屏障转运的策略包括前药脂化方法、顺序新陈代谢化学输送系统、药物载体、脂质体和纳米颗粒。包括讨论如何最大限度地减少网状内皮系统从循环中清除的技术，以延长循环停留时间并优化药物输送系统与血脑屏障之间相互作用的机会。
The brain is protected and isolated from the general circulation by a highly efficient blood-brain barrier. This is characterised by relatively impermeable endothelial cells with tight junctions, enzymatic activity and active efflux transport systems. Consequently the blood-brain barrier is designed to permit selective transport of molecules that are essential for brain function. This creates a considerable challenge for the treatment of central nervous system diseases requiring therapeutic levels of drug to enter the brain. Some small lipophilic drugs diffuse across the blood-brain barrier-sufficiently well to be efficacious. However, many potentially useful drugs are excluded. This review provides an insight into the current research into technologies to target small molecules, peptides and proteins to the brain. A brief review of the nature of the blood-brain barrier and its transport mechanisms is provided. Strategies to target and improve transport across the blood-brain barrier include the prodrug-lipidisation approach, sequential metabolism chemical delivery systems, drug-vectors, liposomes and nanoparticles. Included is the discussion of techniques to minimise clearance from the circulation by the reticuloendothelial system in order to extend circulation residence time and optimise the opportunity for interaction between the drug delivery system and the blood-brain barrier.