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Electrokinetic Convection-Enhanced Delivery of Solutes to the Brain.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-06-19 , DOI: 10.1021/acschemneuro.0c00037 Amir H Faraji 1 , Andrea S Jaquins-Gerstl 1 , Alec C Valenta 1 , Yanguang Ou 1 , Stephen G Weber 1
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-06-19 , DOI: 10.1021/acschemneuro.0c00037 Amir H Faraji 1 , Andrea S Jaquins-Gerstl 1 , Alec C Valenta 1 , Yanguang Ou 1 , Stephen G Weber 1
Affiliation
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Pressure-induced infusion of solutions into brain tissue is used both in research and in medicine. In medicine, convection enhanced delivery (CED) may be used to deliver agents to localized areas of the brain, such as with gene therapy to functional targets or with deep tumors not readily amenable to resection. However, clinical trials have demonstrated mixed results from CED. CED is limited by a lack of control of the infusion flow path and may cause damage or even neurological deficits due to neuronal distortion. In laboratory research, infusions may be achieved using pressure or using brief bursts of electrical current in iontophoresis. Electrokinetic convection enhanced delivery (ECED) has the potential to deliver drugs and other bioactive substances to local regions in the brain with improved control and lower applied pressures than pressure-based CED. ECED improves control over the infusion profile because the fluid follows the electrical current path and thus can be directed. Both small molecules and macromolecules can be delivered. Here we demonstrate proof-of-principal that electrokinetic (electroosmosis and electrophoresis) convection-enhanced delivery is a viable means for delivering solutes to the brain. We assessed the volume of tissue exposed to the infusates tris(2,2′-bipyridine)ruthenium(II) and fluorescent dextrans. Control of the direction of the transport was also achieved over distances ranging from several hundred micrometers to more than 4 mm. Electrokinetic delivery has the potential to improve control over infusions.
中文翻译：
动电对流增强溶质向大脑的输送。
压力诱导的溶液输注到脑组织中既可用于研究，也可用于医学。在医学上，对流增强递送（CED）可用于将药物递送到大脑的局部区域，例如对功能靶标进行基因治疗或对不易切除的深部肿瘤进行治疗。然而，临床试验表明 CED 的结果好坏参半。 CED 由于缺乏对输注流路的控制而受到限制，并且可能因神经元扭曲而导致损伤甚至神经功能缺损。在实验室研究中，可以使用压力或在离子电渗疗法中使用短暂的电流来实现输注。动电对流增强递送 (ECED) 具有将药物和其他生物活性物质递送到大脑局部区域的潜力，与基于压力的 CED 相比，其控制能力得到改善，施加的压力更低。 ECED 改善了对输注曲线的控制，因为流体遵循电流路径，因此可以被引导。小分子和大分子都可以被递送。在这里，我们证明了电动（电渗和电泳）对流增强输送是将溶质输送到大脑的可行方法的原理证明。我们评估了暴露于输注液三(2,2'-联吡啶)钌(II)和荧光葡聚糖的组织体积。还可以在数百微米到超过 4 毫米的距离内实现对传输方向的控制。动电输送有可能改善输液控制。
更新日期：2020-07-15
中文翻译：
动电对流增强溶质向大脑的输送。
压力诱导的溶液输注到脑组织中既可用于研究，也可用于医学。在医学上，对流增强递送（CED）可用于将药物递送到大脑的局部区域，例如对功能靶标进行基因治疗或对不易切除的深部肿瘤进行治疗。然而，临床试验表明 CED 的结果好坏参半。 CED 由于缺乏对输注流路的控制而受到限制，并且可能因神经元扭曲而导致损伤甚至神经功能缺损。在实验室研究中，可以使用压力或在离子电渗疗法中使用短暂的电流来实现输注。动电对流增强递送 (ECED) 具有将药物和其他生物活性物质递送到大脑局部区域的潜力，与基于压力的 CED 相比，其控制能力得到改善，施加的压力更低。 ECED 改善了对输注曲线的控制，因为流体遵循电流路径，因此可以被引导。小分子和大分子都可以被递送。在这里，我们证明了电动（电渗和电泳）对流增强输送是将溶质输送到大脑的可行方法的原理证明。我们评估了暴露于输注液三(2,2'-联吡啶)钌(II)和荧光葡聚糖的组织体积。还可以在数百微米到超过 4 毫米的距离内实现对传输方向的控制。动电输送有可能改善输液控制。
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