School of Biomedical Engineering, University of Western Ontario, 1151 Richmond Str., London, ON N6A 5B9, Canada.
Department of Chemical and Biochemical Engineering, University of Western Ontario, 1151 Richmond Str., London, ON N6A 5B9, Canada.
Int J Mol Sci. 2021 Sep 19;22(18):10118. doi: 10.3390/ijms221810118.
Central nervous system (CNS) diseases are the leading causes of death and disabilities in the world. It is quite challenging to treat CNS diseases efficiently because of the blood-brain barrier (BBB). It is a physical barrier with tight junction proteins and high selectivity to limit the substance transportation between the blood and neural tissues. Thus, it is important to understand BBB transport mechanisms for developing novel drug carriers to overcome the BBB. This paper introduces the structure of the BBB and its physiological transport mechanisms. Meanwhile, different strategies for crossing the BBB by using nanomaterial-based drug carriers are reviewed, including carrier-mediated, adsorptive-mediated, and receptor-mediated transcytosis. Since the viral-induced CNS diseases are associated with BBB breakdown, various neurotropic viruses and their mechanisms on BBB disruption are reviewed and discussed, which are considered as an alternative solution to overcome the BBB. Therefore, most recent studies on virus-mimicking nanocarriers for drug delivery to cross the BBB are also reviewed and discussed. On the other hand, the routes of administration of drug-loaded nanocarriers to the CNS have been reviewed. In sum, this paper reviews and discusses various strategies and routes of nano-formulated drug delivery systems across the BBB to the brain, which will contribute to the advanced diagnosis and treatment of CNS diseases.
中枢神经系统（CNS）疾病是世界范围内导致死亡和残疾的主要原因。由于血脑屏障（BBB）的存在，有效地治疗 CNS 疾病极具挑战性。它是一种具有紧密连接蛋白和高选择性的物理屏障，限制了血液和神经组织之间的物质运输。因此，了解 BBB 的转运机制对于开发新型药物载体以克服 BBB 具有重要意义。本文介绍了 BBB 的结构及其生理转运机制。同时，综述了基于纳米材料的药物载体通过 BBB 的不同策略，包括载体介导、吸附介导和受体介导的转胞吞作用。由于病毒诱导的 CNS 疾病与 BBB 破坏有关，因此还综述和讨论了各种神经嗜性病毒及其破坏 BBB 的机制，这被认为是克服 BBB 的一种替代解决方案。因此，还综述和讨论了用于穿透 BBB 进行药物递送的病毒模拟纳米载体的最新研究。另一方面，还综述了载药纳米载体向 CNS 的给药途径。总之，本文综述和讨论了纳米药物递送系统穿透 BBB 进入大脑的各种策略和途径，这将有助于 CNS 疾病的高级诊断和治疗。
