Convection-enhanced delivery of liposomes to primate brain

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.