使用中空纤维导管改善小分子和病毒载体在小鼠脑内的分布。
Improved distribution of small molecules and viral vectors in the murine brain using a hollow fiber catheter.
作者信息
Oh Seunguk, Odland Rick, Wilson Scott R, Kroeger Kurt M, Liu Chunyan, Lowenstein Pedro R, Castro Maria G, Hall Walter A, Ohlfest John R
机构信息
Department of Neurosurgery, University of Minnesota Medical School, Minneapolis 55455, USA.
出版信息
J Neurosurg. 2007 Sep;107(3):568-77. doi: 10.3171/JNS-07/09/0568.
OBJECT
A hollow fiber catheter was developed to improve the distribution of drugs administered via direct infusion into the central nervous system (CNS). It is a porous catheter that significantly increases the surface area of brain tissue into which a drug is infused.
METHODS
Dye was infused into the mouse brain through convection-enhanced delivery (CED) using a 28-gauge needle compared with a 3-mm-long hollow fiber catheter. To determine whether a hollow fiber catheter could increase the distribution of gene therapy vectors, a recombinant adenovirus expressing the firefly luciferase reporter was injected into the mouse striatum. Gene expression was monitored using in vivo bioluminescent imaging. To assess the distribution of gene transfer, an adenovirus expressing green fluorescent protein was injected into the striatum using a hollow fiber catheter or a needle.
RESULTS
Hollow fiber catheter-mediated infusion increased the volume of brain tissue labeled with dye by 2.7 times relative to needle-mediated infusion. In vivo imaging revealed that catheter-mediated infusion of adenovirus resulted in gene expression that was 10-times greater than that mediated by a needle. The catheter appreciably increased the area of brain transduced with adenovirus relative to a needle, affecting a significant portion of the injected hemisphere.
CONCLUSIONS
The miniature hollow fiber catheter used in this study significantly increased the distribution of dye and adenoviral-mediated gene transfer in the mouse brain compared with the levels reached using a 28-gauge needle. Compared with standard single-port clinical catheters, the hollow fiber catheter has the advantage of millions of nanoscale pores to increase surface area and bulk flow in the CNS. Extending the scale of the hollow fiber catheter for the large mammalian brain shows promise in increasing the distribution and efficacy of gene therapy and drug therapy using CED.
目的
研发一种中空纤维导管，以改善通过直接输注进入中枢神经系统（CNS）的药物分布。它是一种多孔导管，可显著增加药物输注所进入的脑组织表面积。
方法
与使用3毫米长的中空纤维导管相比，通过对流增强递送（CED）使用28号针头将染料注入小鼠脑内。为确定中空纤维导管是否能增加基因治疗载体的分布，将表达萤火虫荧光素酶报告基因的重组腺病毒注入小鼠纹状体。使用体内生物发光成像监测基因表达。为评估基因转移的分布，使用中空纤维导管或针头将表达绿色荧光蛋白的腺病毒注入纹状体。
结果
相对于针头介导的输注，中空纤维导管介导的输注使染料标记的脑组织体积增加了2.7倍。体内成像显示，导管介导的腺病毒输注导致的基因表达比针头介导的高10倍。相对于针头，该导管显著增加了腺病毒转导的脑区面积，影响了注射半球的很大一部分。
结论
与使用28号针头所达到的水平相比，本研究中使用的微型中空纤维导管显著增加了小鼠脑中染料和腺病毒介导的基因转移的分布。与标准的单端口临床导管相比，中空纤维导管具有数百万个纳米级孔隙的优势，可增加中枢神经系统中的表面积和总体流量。将中空纤维导管的规模扩大用于大型哺乳动物脑，有望提高使用CED进行基因治疗和药物治疗的分布和疗效。
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