Though the blood-brain barrier (BBB) is vital for the maintenance of brain homeostasis, it also accounts for a high attrition rate of therapies targeting the central nervous system (CNS). The challenge of delivery across the BBB is attributed to a combination of low permeability through an endothelium closely knit by tight and adherens junctions, extremely low rates of endothelial transcytosis, and efflux transporters. In the past decade, enormous research efforts have been spent to develop BBB penetration strategies using biochemical or physical stimuli, aided by BBB-on-chips or microphysiological BBB models to facilitate in vitro studies. Here, we discuss recent advances in BBB-chip technology that have enabled effective preclinical screenings of brain targeting therapeutics and external stimulation, such as sonoporation and electroporation, for improved BBB penetration.

尽管血脑屏障（BBB）对于维持大脑稳态至关重要，但它也是针对中枢神经系统（CNS）的治疗的高损耗率的原因。跨血脑屏障递送的挑战归因于通过由紧密和粘附连接紧密结合的内皮细胞的低渗透性、极低的内皮转胞吞率和外排转运蛋白的组合。在过去的十年中，人们投入了大量的研究工作来开发使用生化或物理刺激的 BBB 渗透策略，并在 BBB 芯片或微生理 BBB 模型的帮助下促进体外研究。在这里，我们讨论 BBB 芯片技术的最新进展，这些技术能够对大脑靶向治疗和外部刺激（例如声孔和电穿孔）进行有效的临床前筛查，以提高 BBB 渗透。