Delivery of therapeutic agents to the central nervous system is challenged by the barriers in place to regulate brain homeostasis. This is especially true for protein therapeutics. Targeting the barrier formed by the choroid plexuses at the interfaces of the systemic circulation and ventricular system may be a surrogate brain delivery strategy to circumvent the blood-brain barrier. Heterogenous cell populations located at the choroid plexuses provide diverse functions in regulating the exchange of material within the ventricular space. Receptor-mediated transcytosis may be a promising mechanism to deliver protein therapeutics across the tight junctions formed by choroid plexus epithelial cells. However, cerebrospinal fluid flow and other barriers formed by ependymal cells and perivascular spaces should also be considered for evaluation of protein therapeutic disposition. Various preclinical methods have been applied to delineate protein transport across the choroid plexuses, including imaging strategies, ventriculocisternal perfusions, and primary choroid plexus epithelial cell models. When used in combination with simultaneous measures of cerebrospinal fluid dynamics, they can yield important insight into pharmacokinetic properties within the brain. This review aims to provide an overview of the choroid plexuses and ventricular system to address their function as a barrier to pharmaceutical interventions and relevance for central nervous system drug delivery of protein therapeutics. Protein therapeutics targeting the ventricular system may provide new approaches in treating central nervous system diseases.

中文翻译：

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针对蛋白药物输送的脉络膜丛

治疗药物向中枢神经系统的传递受到调节脑稳态的障碍的挑战。对于蛋白质治疗尤其如此。将脉络丛神经形成的屏障靶向全身循环和心室系统的界面可能是替代血脑屏障的替代性大脑递送策略。位于脉络丛的异质细胞群在调节心室空间内的物质交换方面提供了多种功能。受体介导的胞吞作用可能是一种有希望的机制，可以将蛋白治疗剂跨过脉络丛上皮细胞形成的紧密连接传递。然而，脑脊液流动和室管膜细胞和血管周间隙形成的其他障碍也应考虑用于评估蛋白质治疗方案。各种临床前方法已被用来描述跨脉络丛神经的蛋白质转运，包括成像策略，心室胸骨胸腔灌注和原发性脉络丛上皮细胞模型。当与脑脊液动力学的同时测量结合使用时，它们可以对大脑内的药代动力学特性产生重要的见解。这篇综述旨在提供脉络丛和心室系统的概述，以解决其作为药物干预的障碍以及与中枢神经系统药物治疗药物相关性的功能。