Electrophoretic Hybrid Devices for Brain Cancer Therapy

A fundamental limitation for the success of chemotherapy in brain cancer therapies is the blood-brain-barrier which significantly reduces the amount of cancer drugs which can be delivered into a tumour [1]. Bad vascularisation of solid brain tumours further complicates delivery of therapeutically relevant drug doses [2].<br/>Here, we present a novel implantable device which enables highly spatially selective delivery of charged drug molecules directly into brain tumours. Our device combines a microfluidic system for drug transport with embedded electrodes which enable electrophoretic transport of drug molecules into the target tissue. This allows delivery of chemotherapeutic agents without transport of bulk solvent preventing issues arising from intracranial pressure gradients. In order to overcome constraints originating from finite electrode capacities, we have investigated different electrochemical reactions, electrode designs and electric operation modes. We have thereby created a versatile drug delivery system, which is not limited to a specific drug and can easily be adapted to different cancer therapy schedules. The device is uniquely designed for cranial implantation ensuring minimal damage to healthy tissue when implanted. By employing stereolithographic 3D printing for the device fabrication, we allow easy modification of the design to adapt the device driven by individual tumour morphologies. While electrophoretic drug delivery was first described in the early 20^th century and has been used since primarily for transdermal drug delivery, we believe that our approach is one of the first times this has been demonstrated for brain cancer therapy. Electrophoretic delivery will facilitate significantly higher drug concentrations in the tumour tissue than when systemically delivered while having minimal systemic impact.<br/>[1] D. S. Hersh et al. ‘Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier’. In: Current Pharmaceutical Design 22.9 (2016), pp. 1177–1193<br/>[2] J. D. Byrne et al. ‘Local iontophoretic administration of cytotoxic therapies to solid tumors’. In: Science Translational Medicine 7.273 (Feb. 2015), 273ra14–273ra14.