医学
药物输送
从长凳到床边
神经血管束
冲程(发动机)
神经保护
神经科学
中风恢复
药品
血脑屏障
药理学
中枢神经系统
重症监护医学
病理
医学物理学
内科学
纳米技术
康复
物理疗法
机械工程
材料科学
工程类
生物
作者
Patrick T. Ronaldson,Erica I. Williams,Robert D. Betterton,Joshua A Stanton,Kelsy L. Nilles,Thomas P. Davis
出处
期刊:Stroke
[Ovid Technologies (Wolters Kluwer)]
日期:2023-12-22
卷期号:55 (1): 190-202
被引量:3
标识
DOI:10.1161/strokeaha.123.043764
摘要
Drug development for ischemic stroke is challenging as evidenced by the paucity of therapeutics that have advanced beyond a phase III trial. There are many reasons for this lack of clinical translation including factors related to the experimental design of preclinical studies. Often overlooked in therapeutic development for ischemic stroke is the requirement of effective drug delivery to the brain, which is critical for neuroprotective efficacy of several small and large molecule drugs. Advancing central nervous system drug delivery technologies implies a need for detailed comprehension of the blood-brain barrier (BBB) and neurovascular unit. Such knowledge will permit the innate biology of the BBB/neurovascular unit to be leveraged for improved bench-to-bedside translation of novel stroke therapeutics. In this review, we will highlight key aspects of BBB/neurovascular unit pathophysiology and describe state-of-the-art approaches for optimization of central nervous system drug delivery (ie, passive diffusion, mechanical opening of the BBB, liposomes/nanoparticles, transcytosis, intranasal drug administration). Additionally, we will discuss how endogenous BBB transporters represent the next frontier of drug delivery strategies for stroke. Overall, this review will provide cutting edge perspective on how central nervous system drug delivery must be considered for the advancement of new stroke drugs toward human trials.
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