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Temporal and spatial control of drug delivery within the brain using focused ultrasound

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Treatment of primary and metastatic brain tumours remains a major challenge. In particular, limitations due to the incomplete surgical removal, drug side effects and resistance, and the impermeability of the blood-brain barrier (BBB) to most chemotherapeutic drugs together make brain tumours extremely difficult to treat. To this end, a non-invasive and selective strategy that locally increases the permeability of the tumour vascular bed is important for: (i) delivering therapeutic agents at a sufficiently high concentration to the targeted brain tumour, while (ii) minimizing the overall systemic concentration and off-axis side effects. Focused ultrasound (FUS) is currently the only technique that can induce localised opening of the BBB . In combination with ultrasound-responsive lipid ‘packages’ such as liposomes that can transport and prolong the circulation lifetime of cytotoxic drugs, FUS offers a cutting edge potential for targeted brain drug delivery to tumours while minimising systemic side-effects.

Our approach is to apply ultrasound from multielement transducers focused through the skull to the brain target area, combined with liposomes circulating in the blood stream, rendered sensitive to ultrasound by various chemistry specialisations. Our FUS transducers are extracranial, to avoid risks from implanting through the skull, and wearable, so the patient can move freely during treatment. We have achieved proof of concept by observing the behavioural effects of release of dopamine-like drugs from liposomes into deep brain targets, in both rats and sheep. This offers the potential for temporal and spatial control of dopamine replacement in Parkinson’s disease (PD), to stave off the side effects that limit the duration of effectiveness of most PD treatments. In this talk I will review our journey to develop a system for targeted drug delivery for PD that we are now applying to brain tumour treatment, with the vision of ongoing therapy without the repeated need for MRI imaging of the target or surgical implantation

This talk is part of the Electrical Engineering series.

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