Alyautdin Renad, Khalin Igor, Nafeeza Mohd Ismail, Haron Muhammad Huzaimi, Kuznetsov Dmitry
Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh, Selangor, Malaysia.
Faculty of Medicine and Defence Health, National Defence University of Malaysia (NDUM), Kuala Lumpur, Malaysia.
Int J Nanomedicine. 2014 Feb 7;9:795-811. doi: 10.2147/IJN.S52236. eCollection 2014.
The protective properties of the blood-brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport systems expressed on the surface of endothelial cells (ECs) in the brain's vasculature. When the stringent control of the BBB is disrupted, such as following EC damage, substances that are safe for peripheral tissues but toxic to neurons have easier access to the central nervous system (CNS). As a consequence, CNS disorders, including degenerative diseases, can occur independently of an individual's age. Although the BBB is crucial in regulating the biochemical environment that is essential for maintaining neuronal integrity, it limits drug delivery to the CNS. This makes it difficult to deliver beneficial drugs across the BBB while preventing the passage of potential neurotoxins. Available options include transport of drugs across the ECs through traversing occludins and claudins in the tight junctions or by attaching drugs to one of the existing transport systems. Either way, access must specifically allow only the passage of a particular drug. In general, the BBB allows small molecules to enter the CNS; however, most drugs with the potential to treat neurological disorders other than infections have large structures. Several mechanisms, such as modifications of the built-in pumping-out system of drugs and utilization of nanocarriers and liposomes, are among the drug-delivery systems that have been tested; however, each has its limitations and constraints. This review comprehensively discusses the functional morphology of the BBB and the challenges that must be overcome by drug-delivery systems and elaborates on the potential targets, mechanisms, and formulations to improve drug delivery to the CNS.
血脑屏障（BBB）的保护特性是由其内皮细胞的复杂结构以及脑血管系统中内皮细胞（ECs）表面表达的多种特定转运系统赋予的。当血脑屏障的严格控制被破坏时，比如在ECs受损后，对周围组织安全但对神经元有毒的物质更容易进入中枢神经系统（CNS）。因此，包括退行性疾病在内的中枢神经系统疾病可能在个体任何年龄独立发生。尽管血脑屏障在调节维持神经元完整性所必需的生化环境方面至关重要，但它限制了药物向中枢神经系统的递送。这使得在防止潜在神经毒素通过的同时，将有益药物递送至血脑屏障变得困难。现有的选择包括通过穿越紧密连接中的闭合蛋白和 Claudin 蛋白使药物穿过 ECs，或者将药物附着于现有的转运系统之一。无论哪种方式，进入途径都必须只允许特定药物通过。一般来说，血脑屏障允许小分子进入中枢神经系统；然而，大多数有潜力治疗除感染以外的神经系统疾病的药物结构都很大。几种机制，如对药物内置泵出系统的修饰以及纳米载体和脂质体的利用，都属于已测试的药物递送系统；然而，每种机制都有其局限性和制约因素。本综述全面讨论了血脑屏障的功能形态以及药物递送系统必须克服的挑战，并详细阐述了改善药物向中枢神经系统递送的潜在靶点、机制和制剂。
