Blood-brain barrier transport machineries and targeted therapy of brain diseases.
Blood-brain barrier transport machineries and targeted therapy of brain diseases.
复制标题
DOI：
10.15171/bi.2016.30
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Omidi Y
中科院分区：
文献类型：
--
作者：
Barar J;Rafi MA;Pourseif MM;Omidi Y
前言：脑部疾病药物治疗的预期临床结果在很大程度上取决于药物安全地递送到脑实质中。然而，由于血脑屏障（BBB）的强大阻断功能，药物转运到脑中由脑毛细血管内皮细胞形成的BBB选择性地控制，并由星形胶质细胞和周细胞支持。 研究方法：在目前的研究中，我们已经审查了最新的文献上的主题，提供一个深入了解的作用和影响，血脑屏障的脑药物输送和靶向。 结果如下：所有被指定用于治疗脑疾病的药物，无论是小分子还是大分子，都必须充分地穿过BBB，以在中枢神经系统（CNS）内的生物靶点上提供其治疗特性。然而，这些药物中的大多数不能充分渗透到CNS中，不能满足预期的治疗结果。大多数能够穿透血脑屏障的亲脂性药物都倾向于血脑屏障的外排功能。相比之下，所有亲水性药物都面临着由BBB的紧密细胞连接所施加的严重浸润阻断。因此，已经设计了许多策略来提高使用多模态纳米系统（NS）的脑药物递送和CNS疾病的靶向治疗的效率。 结论：为了改善中枢神经系统药物转移和靶向给药的治疗效果，需要控制血脑屏障的区分性通透性。脑毛细血管内皮细胞（BCECs）的载体介导转运机制可用于发现、开发和向脑内递送小分子。此外，受体介导的转运系统可用于将大分子生物制剂和多模式NS递送到脑中。
Introduction: Desired clinical outcome of pharmacotherapy of brain diseases largely depends upon the safe drug delivery into the brain parenchyma. However, due to the robust blockade function of the blood-brain barrier (BBB), drug transport into the brain is selectively controlled by the BBB formed by brain capillary endothelial cells and supported by astrocytes and pericytes. Methods: In the current study, we have reviewed the most recent literature on the subject to provide an insight upon the role and impacts of BBB on brain drug delivery and targeting. Results: All drugs, either small molecules or macromolecules, designated to treat brain diseases must adequately cross the BBB to provide their therapeutic properties on biological targets within the central nervous system (CNS). However, most of these pharmaceuticals do not sufficiently penetrate into CNS, failing to meet the intended therapeutic outcomes. Most lipophilic drugs capable of penetrating BBB are prone to the efflux functionality of BBB. In contrast, all hydrophilic drugs are facing severe infiltration blockage imposed by the tight cellular junctions of the BBB. Hence, a number of strategies have been devised to improve the efficiency of brain drug delivery and targeted therapy of CNS disorders using multimodal nanosystems (NSs). Conclusions: In order to improve the therapeutic outcomes of CNS drug transfer and targeted delivery, the discriminatory permeability of BBB needs to be taken under control. The carrier-mediated transport machineries of brain capillary endothelial cells (BCECs) can be exploited for the discovery, development and delivery of small molecules into the brain. Further, the receptor-mediated transport systems can be recruited for the delivery of macromolecular biologics and multimodal NSs into the brain.