Redox Flow Iontophoresis for Brain Cancer Therapy

Abstract

A fundamental limitation for the success of chemotherapy in brain cancer treatment is the blood brain barrier. It plays a pivotal role in protecting the central nervous system, but also significantly hinders the dose of cancer drugs which can be delivered into a tumour. One option for circumventing the blood brain barrier is implantable iontophoretic devices, which use electric fields for the targeted delivery of charged cancer drugs. However, the performance of these devices suffers from evolution of corrosive gases, detrimental electrochemical reactions of the drug molecules, decreased biocompatibility, and limited device lifetime. Here, I present the results of my PhD research on redox flow iontophoresis, a new approach that I have developed based on the continuous flow of a redox mediator solution to facilitate charge transfer in iontophoretic devices. Redox flow iontophoresis addresses long standing issues of iontophoresis facilitating safe continuous drug delivery for a duration that is theoretic- ally unlimited. To demonstrate the applicability of this technique, I have developed a device designed for cranial implantation directly into brain tumours. Employing stereolithographic 3D printing for the device fabrication allows rapid modification of the design. The device is not limited to specific drug molecules and can therefore easily be adapted to different cancer therapy schedules. I demonstrate that the device is capable of delivering the cancer drug doxorubicin at very high delivery rates of more than 2 nmol/min. Using techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) I demonstrate the excellent compatibility of the implantable device with medical imaging technologies. Further, I present an in vivo study in rodents and canine cancer patients to assess device efficacy in mammals. Redox flow iontophoresis offers a new pathway for targeted drug delivery enabling signi- ficantly higher drug concentrations in tumour tissue than when systemically delivered while maintaining minimal systemic effects. This route therefore promises more effective cancer therapy and improved outcomes.