Krauze Michal T, Forsayeth John, Yin Dali, Bankiewicz Krystof S
Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Methods Enzymol. 2009;465:349-62. doi: 10.1016/S0076-6879(09)65018-7.
Direct delivery of therapeutic agents to the human central nervous system remains an inadequately studied field. Our group has extensively studied and refined a powerful method for distributing various macromolecules and nanoparticles into the parenchyma by means of a procedure called convection-enhanced delivery (CED). First, we developed an improved design of infusion cannula that greatly decreased the likelihood of reflux of infusate up the outside of the cannula. Second, we began to use liposomes loaded with the MRI contrast reagent, Gadoteridol (Gd), to track infusions into brain parenchyma in real time. This innovation generated a wealth of quantitative and qualitative data that in turn drove further improvements in CED. In this chapter, we review many of the recently devised methods needed to ensure controlled distribution of therapeutic agents in the brain.
将治疗药物直接递送至人类中枢神经系统仍是一个研究尚不充分的领域。我们团队广泛研究并改进了一种强大的方法,即通过一种称为对流增强递送(CED)的程序,将各种大分子和纳米颗粒分布到脑实质中。首先,我们开发了一种改进的输注套管设计,大大降低了输注液沿套管外部回流的可能性。其次,我们开始使用装载有磁共振成像(MRI)造影剂钆特醇(Gd)的脂质体,以实时追踪向脑实质内的输注情况。这一创新产生了大量定量和定性数据,进而推动了CED的进一步改进。在本章中,我们回顾了许多为确保治疗药物在脑内实现可控分布而新近设计的方法。