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通过对流增强递送将抗体递送至小鼠脑内。

Delivery of Antibodies into the Murine Brain via Convection-enhanced Delivery.

作者信息

Beffinger Michal, Schellhammer Linda, Pantelyushin Stanislav, Vom Berg Johannes

机构信息

Institute of Laboratory Animal Science, University of Zurich.

Institute of Laboratory Animal Science, University of Zurich;

出版信息

J Vis Exp. 2019 Jul 18(149). doi: 10.3791/59675.

Abstract

Convection-enhanced delivery (CED) is a neurosurgical technique enabling effective perfusion of large brain volumes using a catheter system. Such an approach provides a safe delivery method by-passing the blood brain barrier (BBB), thus allowing treatment with therapeutics with poor BBB-permeability or those for which systemic exposure is not desired, e.g., due to toxicity. CED requires optimization of the catheter design, injection protocol, and properties of the infusate. With this protocol we describe how to perform CED of a solution containing up to 20 µg of an antibody into the caudate putamen of mice. It describes preparation of step catheters, testing them in vitro and performing the CED in mice using a ramping injection program. The protocol can be readily adjusted for other infusion volumes and can be used for injecting various tracers or pharmacologically active or inactive substances, including chemotherapeutics, cytokines, viral particles, and liposomes.

摘要

对流增强递送(CED)是一种神经外科技术,可使用导管系统对大脑的大片区域进行有效灌注。这种方法提供了一种绕过血脑屏障(BBB)的安全递送方式,从而允许使用血脑屏障通透性差的治疗药物或因毒性等原因不希望全身暴露的药物进行治疗。CED需要优化导管设计、注射方案和灌注液的特性。通过本方案,我们描述了如何将含有高达20μg抗体的溶液对流增强递送至小鼠尾状壳核。它描述了阶梯导管的制备、在体外对其进行测试以及使用递增注射程序在小鼠中进行CED。该方案可轻松针对其他输注体积进行调整,并可用于注射各种示踪剂或药理活性或无活性物质,包括化疗药物、细胞因子、病毒颗粒和脂质体。

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