Real-time monitoring of ultrasound and cavitation mediated drug delivery

Drug delivery plays a crucial role in the chemotherapeutic treatment of cancerous solid tumours. A drug, no matter how potent, is only truly effective when it can be delivered to all targeted cells. In recent years it has been recognised that the poor response of tumours to chemotherapy is in part due to inadequate drug delivery. Numerous strategies have been developed to overcome this issue. Of particular interest to the present work is the application of ultrasound and cavitation, which has been shown to be capable of enhancing drug delivery in solid tumours. These enhancements are attributed to the acoustic cavitation of microbubbles and the effects cavitation induces in the surrounding tissue. To better understand how ultrasound and cavitation can enhance drug delivery, an instrument was developed that is capable of monitoring in real-time and in-situ the effect of ultrasound and cavitation on drugs and drug analogues within flow channel models. The developed instrument was used to investigate the effect of ultrasound and cavitation on drug-eluting beads used for chemoembolisation, the effects of drug loading on microbubble dynamics, the effects produced by different cavitation agents, and the performance of passive acoustic mapping as a means of cavitation monitoring. The findings of the above investigations include: more physiologically relevant characterisations of drug-eluting beads pharmacokinetics, the possibility of significant changes in microbubble dynamics due to drug loading, a lack of general correlation between detected cavitation activity and induced effects, and the potential of passive acoustic mapping for monitoring cavitation and ultrasound induced effects. These and other findings also demonstrate the utility of the developed instrument for studying the many facets and applications of ultrasound and cavitation mediated drug delivery.