Department of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, Texas, 76107, USA.
Curr Drug Deliv. 2022;19(10):1034-1046. doi: 10.2174/1567201819666220303102614.
Disorders of the brain constitute the most debilitating situation globally with increased mortality rates every year, while brain physiology and cumbersome drug development processes exacerbate this. Although blood-brain barrier (BBB) and its components are important for brain protection, their complexity creates major obstacles for brain drug delivery, and the BBB is the primary cause of treatment failure, leading to disease progression. Therefore, developing an ideal platform that can predict the behavior of a drug delivery system in the brain at the early development phase is extremely crucial. In this direction, in the last two decades, numerous in vitro BBB models have been developed and investigated by researchers to understand the barrier properties and how closely the in vitro models mimic in vivo BBB. In-vitro BBB models mainly involve the culture of endothelial cells or their coculture with other perivascular cells either in two or three-dimensional platforms. In this article, we have briefly summarized the fundamentals of BBB and outlined different types of in vitro BBB models with their pros and cons. Based on the available reports, no model seems to be robust that can truly mimic the entire properties of the in vivo BBB microvasculature. However, human stem cells, coculture and threedimensional models have been found to mimic the complexity of the barrier integrity not completely but more precisely than other in vitro models. More studies aiming towards combining these models together would be needed to develop an ideal in vitro model that can overcome the existing limitations and unravel the mysterious BBB vasculature.
大脑障碍是全球最具危害性的疾病之一，每年的死亡率都在上升，而大脑生理学和繁琐的药物开发过程使情况更加恶化。尽管血脑屏障 (BBB) 及其组成部分对大脑保护很重要，但它们的复杂性给脑内药物输送带来了重大障碍，而 BBB 是治疗失败的主要原因，导致疾病进展。因此，开发一种理想的平台，能够在早期开发阶段预测药物输送系统在大脑中的行为，是极其关键的。在这方面，在过去的二十年中，研究人员已经开发并研究了许多体外 BBB 模型，以了解屏障特性以及体外模型与体内 BBB 的相似度。体外 BBB 模型主要涉及内皮细胞的培养或与其他血管周细胞的共培养，无论是在二维还是三维平台上。在本文中，我们简要总结了 BBB 的基础知识，并概述了不同类型的体外 BBB 模型及其优缺点。根据现有报道，似乎没有一种模型能够真正模拟体内 BBB 微血管的全部特性，是稳健的。然而，已经发现人类干细胞、共培养和三维模型比其他体外模型更能模拟屏障完整性的复杂性，尽管不是完全模拟。需要更多旨在将这些模型结合在一起的研究，以开发出一种理想的体外模型，克服现有局限性，揭示神秘的 BBB 血管系统。
