血脑屏障开放方法研究进展

Advances in strategies to overcome the blood-brain barrier

治疗中枢神经系统疾病药物研发失败的主要原因之一是由于血脑屏障的阻碍作用,使得药物无法递送到中枢神经系统,未能在脑内聚积达到足够的药效剂量和产生相应的治疗作用。因此,中枢靶向药物研发成功的一个关键因素就是需要克服血脑屏障,这使得研究开放血脑屏障的方法成为脑内给药的热点。本文综述了近10余年研究和应用促进药物透过血脑屏障的手段,探索各种药物载体的给药策略,并详细阐述了开放血脑屏障的研究方法,为开发新型中枢靶向药物提供思路和帮助。本文认为从血脑屏障的结构特点入手,研究血脑屏障开放机制,深入了解转运系统、转运载体和细胞信号转导通路,设计更有效开放血脑屏障的策略,才能实现药物安全、高效、可控地透过血脑屏障,在脑内发挥治疗作用。

A major reason for the failure of research and development for central nevous system（CNS） agents and acetylcholin- esterase reactivators is their inability to cross blood-brain barrier （BBB） to reach the brain. Mostly available agents have limited perme- ability via BBB to effectively treat CNS disorders. Hence, the major challenge in agents development and delivery for the neurological diseases is to overcome the main impediment for the brain agents delivery. In this review, we summarize each of these approaches, highlight their successes and obstacles, discuss transporters of potential targets for brain agents delivery, and provide an insight into some of recent advances made in brain agents delivery, in order to improve the potential utility of these compounds in therapeutics. The present review suggests that based on the structure and function of BBB, future work continue to focus more closely on molecular mechanisms that affect brain permeation, transporters and intracellular signaling pathways. Ultimately, the achievement of these stud- ies is to find safe and effective delivery strategies for administering agents to the brain and playing a therapeutic role.