Department of Mechanical Engineering, The University of Texas at Dallas, Richardson, TX 75080.
Department of Mechanical Engineering, The University of Texas at Dallas, Richardson, TX 75080; Department of Bioengineering, The University of Texas at Dallas, Richardson, TX 75080; Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390; Center for Advanced Pain Studies, The University of Texas at Dallas, Richardson, TX 75080.
J Biomech Eng. 2023 Aug 1;145(8). doi: 10.1115/1.4062737.
The blood-brain barrier (BBB) is a dynamic regulatory barrier at the interface of blood circulation and the brain parenchyma, which plays a critical role in protecting homeostasis in the central nervous system. However, it also significantly impedes drug delivery to the brain. Understanding the transport across BBB and brain distribution will facilitate the prediction of drug delivery efficiency and the development of new therapies. To date, various methods and models have been developed to study drug transport at the BBB interface, including in vivo brain uptake measurement methods, in vitro BBB models, and mathematic brain vascular models. Since the in vitro BBB models have been extensively reviewed elsewhere, we provide a comprehensive summary of the brain transport mechanisms and the currently available in vivo methods and mathematic models in studying the molecule delivery process at the BBB interface. In particular, we reviewed the emerging in vivo imaging techniques in observing drug transport across the BBB. We discussed the advantages and disadvantages associated with each model to serve as a guide for model selection in studying drug transport across the BBB. In summary, we envision future directions to improve the accuracy of mathematical models, establish noninvasive in vivo measurement techniques, and bridge the preclinical studies with clinical translation by taking the altered BBB physiological conditions into consideration. We believe these are critical in guiding new drug development and precise drug administration in brain disease treatment.
血脑屏障（BBB）是血液循环和脑实质界面上的动态调节屏障，在保护中枢神经系统内环境稳定方面起着至关重要的作用。然而，它也极大地阻碍了药物向大脑的输送。了解药物通过 BBB 的转运和在脑内的分布情况，将有助于预测药物输送的效率并开发新的治疗方法。迄今为止，已经开发出各种方法和模型来研究 BBB 界面处的药物转运，包括体内脑摄取测量方法、体外 BBB 模型和数学脑血管模型。由于体外 BBB 模型已在其他地方进行了广泛的综述，因此我们全面总结了脑转运机制以及目前用于研究分子在 BBB 界面处传递过程的体内可用方法和数学模型。特别是，我们综述了观察药物穿过 BBB 转运的新兴体内成像技术。我们讨论了每种模型的优缺点，以作为在研究药物穿过 BBB 转运时选择模型的指南。总之，我们设想了未来的方向，以提高数学模型的准确性，建立非侵入性的体内测量技术，并通过考虑改变的 BBB 生理条件将临床前研究与临床转化联系起来。我们相信这些对于指导新药开发和脑疾病治疗中的精确药物给药至关重要。
