Cai Yicong, Fan Kexin, Lin Jiawei, Ma Lin, Li Fenfang
Shenzhen Bay Laboratory, Institute of Biomedical Engineering, Shenzhen 518107, China.
School of Physics and Optoelectronic Engineering, Guangdong University of Technology, Guangzhou 510006, China.
Micromachines (Basel). 2022 Dec 30;14(1):112. doi: 10.3390/mi14010112.
The complex structure of the blood-brain barrier (BBB), which blocks nearly all large biomolecules, hinders drug delivery to the brain and drug assessment, thus decelerating drug development. Conventional in vitro models of BBB cannot mimic some crucial features of BBB in vivo including a shear stress environment and the interaction between different types of cells. There is a great demand for a new in vitro platform of BBB that can be used for drug delivery studies. Compared with in vivo models, an in vitro platform has the merits of low cost, shorter test period, and simplicity of operation. Microfluidic technology and microfabrication are good tools in rebuilding the BBB in vitro. During the past decade, great efforts have been made to improve BBB penetration for drug delivery using biochemical or physical stimuli. In particular, compared with other drug delivery strategies, sonoporation is more attractive due to its minimized systemic exposure, high efficiency, controllability, and reversible manner. BBB on chips (BOC) holds great promise when combined with sonoporation. More details and mechanisms such as trans-endothelial electrical resistance (TEER) measurements and dynamic opening of tight junctions can be figured out when using sonoporation stimulating BOC, which will be of great benefit for drug development. Herein, we discuss the recent advances in BOC and sonoporation for BBB disruption with this in vitro platform.
血脑屏障（BBB）结构复杂，几乎能阻挡所有大分子，这阻碍了药物向脑部的递送及药物评估，进而延缓了药物研发进程。传统的血脑屏障体外模型无法模拟体内血脑屏障的一些关键特征，包括剪切应力环境以及不同类型细胞之间的相互作用。因此，迫切需要一种可用于药物递送研究的新型血脑屏障体外平台。与体内模型相比，体外平台具有成本低、测试周期短和操作简便等优点。微流控技术和微加工是体外重建血脑屏障的良好工具。在过去十年中，人们致力于通过生化或物理刺激来提高药物递送对血脑屏障的穿透性。特别是，与其他药物递送策略相比，声孔效应因其全身暴露最小化、高效、可控且可逆等特点而更具吸引力。芯片上的血脑屏障（BOC）与声孔效应相结合时前景广阔。使用声孔效应刺激BOC时，可以弄清楚更多细节和机制，如跨内皮电阻（TEER）测量和紧密连接的动态开放，这将对药物研发大有裨益。在此，我们讨论了利用这个体外平台在BOC和声孔效应用于破坏血脑屏障方面的最新进展。
