DDEL-12: A SYSTEM BASED APPROACH TO CHRONIC DRUG DELIVERY - A METHOD THAT WORKS

Published retrospective analysis of failed clinical trials that have utilised Convection-Enhanced Delivery (CED) as the infusion mechanism have highlighted that a small number of system elements (targeting, device design, lack of real-time imaging etc.) can cause poor outcomes and prevent primary trial objectives being met. A limited number of systems exist for acute, stereotactically guided delivery but systems and strategies for longer term applications are lacking. The problem of achieving controlled intermittent delivery to the brain must therefore be tackled at the system level. Through a collaborative relationship between research and industry it has been possible to bring together multidisciplinary teams and implement a lab to clinic development paradigm. Engineering developments in surgical planning software, rigid tooling and surgical robotics have laid a solid foundation on which to improve surgical techniques, implant design and external re-access kits. Investigation of a guide tube catheter assembly was conducted first in the Agarose gel model and later in the porcine and canine model to help inform surgical planning strategies. Catheter design features were manipulated as a variable to induce changes in the infusion morphology and were investigated over time. Methods for ongoing distribution optimisation were also reviewed. Acquisition of anatomical targets ∼120mm deep can now be achieved sub millimetre utilising the surgical system. Greater coverage of anatomical structures is possible through device modifications which effect changes to the infusion morphology. Ongoing optimisation of infusions might be achieved through periodic imaging and implementing improved, patient specific infusion regimes. A multidisciplinary approach to the problem of chronic implantation is required to achieve successful intermittent infusions in the brain.