Targeting the Choroid Plexuses for Protein Drug Delivery.
Targeting the Choroid Plexuses for Protein Drug Delivery.
复制标题
靶向脉络丛用于蛋白质药物递送。
DOI：
10.3390/pharmaceutics12100963
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发表时间：
2020-10-14
期刊：
影响因子：
5.4
通讯作者：
Morris ME
中科院分区：
文献类型：
--
作者：
Bryniarski MA;Ren T;Rizvi AR;Snyder AM;Morris ME
治疗药物向中枢神经系统的输送受到了调节大脑内稳态的障碍的挑战。对于蛋白质疗法来说，情况尤其如此。以脉络丛在体循环和脑室系统交界处形成的屏障为靶点可能是一种绕过血脑屏障的替代脑递送策略。位于脉络丛处的异质细胞群在调节脑室间隙内物质交换方面具有不同的功能。受体介导的细胞转运可能是一种很有前途的机制，可以通过脉络丛上皮细胞形成的紧密连接传递蛋白质治疗药物。然而，脑脊液流动和其他由室管膜细胞和血管周围间隙形成的屏障也应该被考虑到蛋白质治疗倾向的评估。不同的临床前方法已经被应用于描述蛋白质在脉络丛中的运输，包括成像策略、脑室池灌注和原代脉络丛上皮细胞模型。当与脑脊液动力学的同步测量结合使用时，它们可以对大脑内的药代动力学特性产生重要的洞察。该综述旨在提供脉络丛和脑室系统的概述，以说明它们作为药物干预的屏障的功能以及与中枢神经系统蛋白质疗法药物输送的相关性。针对脑室系统的蛋白质疗法可能为治疗中枢神经系统疾病提供新的方法。
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.
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