Designing and Testing of Backflow-Free Catheters

Abstract

Convection-enhanced delivery (CED) is a drug delivery technique used to target specific regions of the central nervous system (CNS) for the treatment of neurodegenerative diseases and cancer while bypassing the blood-brain barrier (BBB). The application of CED is limited by low volumetric flow rate infusions in order to prevent the possibility of backflow. Consequently, a small convective flow produces poor drug distribution inside the treatment region, which can render CED treatment ineffective. Novel catheter designs and CED protocols are needed in order to improve the drug distribution inside the treatment region and prevent backflow. In order to develop novel backflow-free catheter designs, the impact of the micro-fluid injection into deformable porous media was investigated experimentally as well as numerically. Fluid injection into the porous media has a considerable effect on local transport properties such as porosity and hydraulic conductivity because of the local media deformation. These phenomena not only alter the bulk flow velocity distribution of the micro-fluid flow due to the changing porosity, but significantly modify the flow direction, and even the volumetric flow distribution, due to induced local hydraulic conductivity anisotropy. These findings help us to design backflow-free catheters with safe volumetric flow rates up to 10 μl/min. A first catheter design reduces porous media deformation in order to improve catheter performance and control an agent volumetric distribution. A second design prevents the backflow by reducing the porosity and hydraulic conductivity along a catheter's shaft. A third synergistic catheter design is a combination of two previous designs. Novel channel-inducing and dual-action catheters, as well as a synergistic catheter, were successfully tested without the occurrence of backflow and are recommended for future animal experiments.