Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA.
Carbone Cancer Center, School of Medicine & Public Health, University of Wisconsin, Madison, WI 53792, USA.
Nanomedicine (Lond). 2018 Sep;13(18):2327-2340. doi: 10.2217/nnm-2018-0084. Epub 2018 Oct 4.
Ischemic stroke is a leading cause of death and disability worldwide and is in urgent need of new treatment options. The only approved treatment for stroke restores blood flow to the brain, but much of the tissue damage occurs during the subsequent reperfusion. Antioxidant therapies that directly address ischemia-reperfusion injury have shown promise in preclinical results. In this review, we discuss that reformulating antioxidant therapies as nanomedicine can potentially overcome the barriers that have kept these therapies from succeeding in the clinic. We begin by reviewing the pathophysiology of ischemic stroke with a focus on the effects of reperfusion injury. Next, we review nanotherapeutic systems designed to treat the disease with a focus on those addressing reperfusion injury. Mechanisms of passive and active transport required to traverse a blood-brain barrier are discussed. Finally, we conclude by outlining design parameters for potentially successful nanomedicines as front-line therapeutics for ischemic stroke.
缺血性脑卒中是全球范围内主要的致死和致残原因，迫切需要新的治疗选择。目前唯一被批准的脑卒中治疗方法是恢复脑部血流，但在随后的再灌注过程中，大部分组织损伤已经发生。在临床前研究结果中，直接针对缺血再灌注损伤的抗氧化治疗显示出了良好的效果。在这篇综述中，我们讨论了将抗氧化治疗重新设计成纳米医学，可能会克服这些治疗方法在临床上未能成功的障碍。我们首先回顾了缺血性脑卒中的病理生理学，重点讨论了再灌注损伤的影响。接下来，我们回顾了旨在治疗这种疾病的纳米治疗系统，重点讨论了那些针对再灌注损伤的系统。讨论了穿越血脑屏障所需的被动和主动转运机制。最后，我们通过概述可能成功的纳米药物的设计参数，为缺血性脑卒中的一线治疗方法做了总结。
