Redox flow iontophoresis for continuous drug delivery

Abstract

Drug delivery into the brain and spinal cord is fundamentally limited by the blood brain barrier which impedes the use of the vast majority of drugs. Implants based on iontophoresis use an applied voltage to deliver charged drug molecules, allowing solvent-free delivery directly into the site of interest and overcoming issues associated with systemic exposure to the drug. However, during continuous delivery over long periods, electrochemical reactions occur at the electrodes leading to corrosive gas formation. Here, we present the concept of redox flow iontophoresis, where a redox mediator solution is used to control electrode reactions and sustain continuous delivery for theoretically unlimited duration. As a proof-of-concept, we demonstrate a redox flow iontophoresis-based brain implant which can continuously deliver the cancer drug doxorubicin at stable rates exceeding 2 nmol/min. This new concept enables the continuous delivery of various potent drugs into the brain and spinal cord and therefore has the potential to improve treatment options for various diseases.