Fukuta Tatsuya, Oku Naoto, Kogure Kentaro
Department of Physical Pharmaceutics, School of Pharmaceutical Sciences, Wakayama Medical University, 25-1 Shichiban-cho, Wakayama 640-8156, Japan.
Faculty of Pharma-Science, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Pharmaceutics. 2022 Feb 4;14(2):361. doi: 10.3390/pharmaceutics14020361.
Ischemic stroke is still one of the leading causes of high mortality and severe disability worldwide. Therapeutic options for ischemic stroke and subsequent cerebral ischemia/reperfusion injury remain limited due to challenges associated with drug permeability through the blood-brain barrier (BBB). Neuroprotectant delivery with nanoparticles, including liposomes, offers a promising solution to address this problem, as BBB disruption following ischemic stroke allows nanoparticles to pass through the intercellular gaps between endothelial cells. To ameliorate ischemic brain damage, a number of nanotherapeutics encapsulating neuroprotective agents, as well as surface-modified nanoparticles with specific ligands targeting the injured brain regions, have been developed. Combination therapy with nanoparticles encapsulating neuroprotectants and tissue plasminogen activator (t-PA), a globally approved thrombolytic agent, has been demonstrated to extend the narrow therapeutic time window of t-PA. In addition, the design of biomimetic drug delivery systems (DDS) employing circulating cells (e.g., leukocytes, platelets) with unique properties has recently been investigated to overcome the injured BBB, utilizing these cells' inherent capability to penetrate the ischemic brain. Herein, we review recent findings on the application and utility of nanoparticle DDS, particularly liposomes, and various approaches to developing biomimetic DDS functionalized with cellular membranes/membrane proteins for the treatment of ischemic stroke.
缺血性中风仍然是全球高死亡率和严重残疾的主要原因之一。由于药物透过血脑屏障（BBB）存在挑战，缺血性中风及随后的脑缺血/再灌注损伤的治疗选择仍然有限。包括脂质体在内的纳米颗粒递送神经保护剂为解决这一问题提供了一个有前景的解决方案，因为缺血性中风后血脑屏障的破坏使纳米颗粒能够穿过内皮细胞之间的细胞间隙。为了改善缺血性脑损伤，已经开发了许多包裹神经保护剂的纳米疗法，以及具有靶向损伤脑区的特异性配体的表面修饰纳米颗粒。已证明将包裹神经保护剂的纳米颗粒与组织纤溶酶原激活剂（t-PA，一种全球批准的溶栓剂）联合治疗可延长t-PA狭窄的治疗时间窗。此外，最近研究了利用具有独特特性的循环细胞（如白细胞、血小板）设计仿生药物递送系统（DDS），以克服受损的血脑屏障，利用这些细胞穿透缺血性脑的固有能力。在此，我们综述了纳米颗粒DDS，特别是脂质体的应用和效用的最新发现，以及开发用细胞膜/膜蛋白功能化的仿生DDS治疗缺血性中风的各种方法。
