Oladosu Folabomi A, Ciszek Brittney P, O'Buckley Sandra C, Nackley Andrea G
Curriculum of Neurobiology, University of North Carolina, Chapel Hill, 27599 NC, USA.
Curriculum of Oral Biology, University of North Carolina, Chapel Hill, 27599 NC, USA.
J Neurosci Methods. 2016 May 1;264:119-128. doi: 10.1016/j.jneumeth.2016.03.006. Epub 2016 Mar 11.
Catheter systems that permit targeted delivery of genes, molecules, ligands, and other agents represent an investigative tool critical to the development of clinically relevant animal models that facilitate the study of neurological health and disease. The development of new sustained catheter delivery systems to spinal and peripheral sites will reduce the need for repeated injections, while ensuring constant levels of drug in plasma and tissues.
Here, we introduce two novel catheter delivery systems in the mouse: the O'Buckley intrathecal catheter system for sustained delivery to the spinal region and a subcutaneous bifurcated catheter system for sustained drug delivery to both hindpaws.
The O'Buckley intrathecal catheter system consistently distributed Evans Blue throughout the spinal cord, with the greatest concentration at the thoracic region, and with an 85% surgery success rate. The subcutaneous catheter system consistently distributed Evans Blue to the hindlimbs, with a 100% surgery success rate.
The O'Buckley intrathecal catheter system accomplishes sustained drug delivery to the spinal region, with a 2-fold increase in surgery success rate, as compared to the traditional method. Our subcutaneous bifurcated catheter system accomplishes sustained drug delivery to both hindpaws, eliminating the need for repeated intraplantar injections.
We have developed catheter systems that improve upon traditional methods in order to achieve sustained localized drug delivery to spinal tissues and to hindpaw tissues surrounding peripheral sciatic nerve terminals. These methods have a broad reach, and can be used to enhance behavioral, physiologic and mechanistic studies in mice.
能够实现基因、分子、配体及其他药剂靶向递送的导管系统,是开发有助于研究神经健康与疾病的临床相关动物模型的关键研究工具。开发新型的可将药物持续递送至脊髓和外周部位的导管系统,将减少重复注射的需求,同时确保血浆和组织中的药物水平恒定。
在此,我们在小鼠中引入了两种新型导管递送系统:用于向脊髓区域持续给药的奥巴克利鞘内导管系统,以及用于向后肢双足持续给药的皮下分叉导管系统。
奥巴克利鞘内导管系统能持续将伊文思蓝分布于整个脊髓,在胸段浓度最高,手术成功率为85%。皮下导管系统能持续将伊文思蓝分布于后肢,手术成功率为100%。
与传统方法相比,奥巴克利鞘内导管系统实现了向脊髓区域的持续药物递送,手术成功率提高了两倍。我们的皮下分叉导管系统实现了向后肢双足的持续药物递送,无需进行重复的足底注射。
我们开发的导管系统对传统方法进行了改进,以实现向脊髓组织以及坐骨神经末梢周围的后爪组织持续局部给药。这些方法具有广泛的应用范围,可用于加强对小鼠的行为、生理和机制研究。