Infusion and iontophoresis for directional delivery of compounds to the brain

Abstract

Convection-enhanced delivery enables local administration of therapeutic agents to brain tissues by overcoming the challenges posed by the blood-brain barrier. However, its efficacy is limited by the lack of control over the delivery pathway. To address this, we propose infusion and iontophoresis for directional delivery of compounds in the brain (IIDD). This IIDD strategy involves the insertion of a cannula for drug infusion, along with two plateshaped electrodes serving as the cathode and anode and positioned at predetermined sites in the brain. Iontophoresis generates an electrical path for controlled, directional transport of the injected compound. We tested it with gadobutrol, a clinically approved, negatively charged gadolinium-based contrast agent. We observed that increasing the duration of application of current (fixed current of 10 mu A) facilitated significantly better migration of gadobutrol toward the anode than simple diffusion by convection-enhanced delivery alone. Simulation data derived from three-dimensional finite element modeling were consistent with the experimental findings. This further confirmed the feasibility of infusion and iontophoresis for directional delivery of compounds in the brain.