Bioengineering Seminar Series
"Targeting, Enhancement and Monitoring of Drug Delivery by Ultrasound"
Constantin Coussios, PhD
Professor of Bioengineering
University of Oxford
Achieving delivery of an adequate and spatially uniform concentration of therapeutic agents in inaccessible biological targets such as tumours or blood clots has presented a major challenge to the pharmaceutical industry for decades. In cancer therapy in particular, intratumoural pressure, low perfusion, hypoxia, irregular vasculature and the greater distance between cancer cells and the nearest blood vessel represent major barriers for drug delivery. Yet ultrasound has the potential to overcome all of these difficulties. Encapsulation of potent drugs in liposomal or polymeric vesicles can enable improved targeting and pharmacokinetics, and localized release of the drug through ultrasound-mediated thermal and mechanical effects. But perhaps the greatest role for ultrasound to play is in the extravasation of either a free or an encapsulated drug through the endothelial wall into surrounding tissues: inertial cavitation was recently shown to enable the delivery of large molecular compounds to hundreds of microns from the nearest blood vessel. Last but not least, if cavitation is exploited as a key delivery mechanism, it can also be mapped using a novel technique developped in Oxford, known as Passive Acoustic Mapping (PAM): this makes it possible to provide information to clinicians as to where and when a drug has been successfully delivered in real time. Cavitation-enhanced drug delivery mediated by ultrasound and guided by PAM will be illustrated in the context of doxorubicin delivery from thermosensitive liposomes, and also in the context of delivery of oncolytic adenoviruses for highly selective cancer therapy.