Targeting blood-brain barrier changes during inflammatory pain: an opportunity for optimizing CNS drug delivery.
Targeting blood-brain barrier changes during inflammatory pain: an opportunity for optimizing CNS drug delivery.
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DOI：
10.4155/tde.11.67
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发表时间：
2011-08
影响因子：
4.2
通讯作者：
Davis TP
中科院分区：
文献类型：
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作者：
Ronaldson PT;Davis TP
血脑屏障(BBB)是影响中枢神经系统药物有效传递的最大障碍。它具有限制外源生物渗透的结构和生化特征(即紧密连接的蛋白质复合体以及流入和流出转运体)。病理生理应激源(即外周炎性疼痛)可以改变血脑屏障紧密连接和转运蛋白，从而导致药物渗透性的改变。这对阿片类药物尤其关键，因为阿片类药物需要精确的中枢神经系统浓度才能成为安全有效的镇痛剂。最近的研究已经确定了可用于优化中枢神经系统药物传递的分子靶点(即内源性转运体和细胞内信号系统)。本文总结了这一领域的现有知识，并强调了那些最有可能控制药物渗透和/或药物跨血脑屏障转运的目标，以努力实现中枢阿片类药物的最佳给药。
The blood–brain barrier (BBB) is the most significant obstacle to effective CNS drug delivery. It possesses structural and biochemical features (i.e., tight-junction protein complexes and, influx and efflux transporters) that restrict xenobiotic permeation. Pathophysiological stressors (i.e., peripheral inflammatory pain) can alter BBB tight junctions and transporters, which leads to drug-permeation changes. This is especially critical for opioids, which require precise CNS concentrations to be safe and effective analgesics. Recent studies have identified molecular targets (i.e., endogenous transporters and intracellular signaling systems) that can be exploited for optimization of CNS drug delivery. This article summarizes current knowledge in this area and emphasizes those targets that present the greatest opportunity for controlling drug permeation and/or drug transport across the BBB in an effort to achieve optimal CNS opioid delivery.