The penetration of therapeutics across the blood-brain barrier: Classic case studies and clinical implications.

IF 11.7 1区 医学 Q1 CELL BIOLOGY Cell Reports Medicine Pub Date : 2024-10-03 DOI:10.1016/j.xcrm.2024.101760
William A Banks, Elizabeth M Rhea, May J Reed, Michelle A Erickson
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Abstract

The blood-brain barrier (BBB) plays central roles in the maintenance and health of the brain. Its mechanisms to safeguard the brain against xenobiotics and endogenous toxins also make the BBB the primary obstacle to the development of drugs for the central nervous system (CNS). Here, we review classic examples of the intersection of clinical medicine, drug delivery, and the BBB. We highlight the role of lipid solubility (heroin), saturable brain-to-blood (efflux: opiates) and blood-to-brain (influx: nutrients, vitamins, and minerals) transport systems, and adsorptive transcytosis (viruses and incretin receptor agonists). We examine how the disruption of the BBB that occurs in certain diseases (tumors) can also be modulated (osmotic agents and microbubbles) and used to deliver treatments, and the role of extracellular pathways in gaining access to the CNS (albumin and antibodies). In summary, this review provides a historical perspective of the key role of the BBB in delivery of drugs to the brain in health and disease.

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治疗药物穿越血脑屏障:经典案例研究与临床意义。
血脑屏障(BBB)在维护大脑健康方面发挥着核心作用。它保护大脑免受外来生物和内源性毒素侵害的机制也使 BBB 成为开发中枢神经系统(CNS)药物的主要障碍。在此,我们将回顾临床医学、药物输送和 BBB 相互交叉的经典案例。我们强调了脂溶性(海洛因)、可饱和脑-血(流出:阿片剂)和血-脑(流入:营养素、维生素和矿物质)转运系统以及吸附性转囊(病毒和增量素受体激动剂)的作用。我们还研究了如何调节某些疾病(肿瘤)导致的 BBB 破坏(渗透剂和微气泡)并利用其进行治疗,以及细胞外途径在进入中枢神经系统中的作用(白蛋白和抗体)。总之,本综述从历史的角度阐述了 BBB 在健康和疾病情况下向大脑输送药物的关键作用。
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来源期刊
Cell Reports Medicine
Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
15.00
自引率
1.40%
发文量
231
审稿时长
40 days
期刊介绍: Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.
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