Electrokinetic Convection-Enhanced Delivery of Solutes to the Brain.

Abstract

Pressure-induced infusion of solutions into brain tissue is used both in research and in medicine. In medicine, convection enhanced delivery (CED) may be used to deliver agents to localized areas of the brain, such as with gene therapy to functional targets or with deep tumors not readily amenable to resection. However, clinical trials have demonstrated mixed results from CED. CED is limited by a lack of control of the infusion flow path and may cause damage or even neurological deficits due to neuronal distortion. In laboratory research, infusions may be achieved using pressure or using brief bursts of electrical current in iontophoresis. Electrokinetic convection enhanced delivery (ECED) has the potential to deliver drugs and other bioactive substances to local regions in the brain with improved control and lower applied pressures than pressure-based CED. ECED improves control over the infusion profile because the fluid follows the electrical current path and thus can be directed. Both small molecules and macromolecules can be delivered. Here we demonstrate proof-of-principal that electrokinetic (electroosmosis and electrophoresis) convection-enhanced delivery is a viable means for delivering solutes to the brain. We assessed the volume of tissue exposed to the infusates tris(2,2'-bipyridine)ruthenium(II) and fluorescent dextrans. Control of the direction of the transport was also achieved over distances ranging from several hundred micrometers to more than 4 mm. Electrokinetic delivery has the potential to improve control over infusions.