Wed September 23rd 2015
16:00 – 17:00
ZH286
Seminar Cavitation-Enhanced Drug Delivery: Microscale Transport from Nanoscale Particles
Constantin Coussios

Details:

The majority of studies to date on cavitation-mediated drug delivery have focussed on interactions between single bubbles and individual cells, focussing primarily on interactions with the cell membrane. The potentially beneficial role of cavitation in enhancing transport and delivery of small molecules and nanomedicines to more complex tissue structures, such as tumours, has received significantly less attention, not least because of the inability of optical methods to map cavitation activity in bulk tissue.

We first present a novel method, termed Passive Acoustic Mapping (PAM), developed to enable real-time characterization and quantification of cavitation activity from multiple cavitating regions in tissue using an array of ultrasound transducers. The method is first validated in vitro in agar phantoms, demonstrating an ability to identify phenomena such as period doubling and period tripling occurring simultaneously. Further developments of the beamforming algorithms then enables deployment of the method in vivo, where cavitation activity can be mapped and quantified in real time in whole tumours.

By taking advantage of PAM for quantifying cavitation activity in complex tissue structures, the effect of cavitation on transport of nanoparticles is investigated. It is first demonstrated that the occurrence of cavitation-induced microstreaming in blood vessels enables the transport of nanomedicines to hundreds of microns from the vessel wall, but that this occurs only in the presence of inertial rather than non-inertial cavitation. This observation motivates two further lines of investigation: the need to develop cavitation nuclei which are capable of ‘following’ drug molecules into tumours, rather than being confined to the vasculature; and the opportunity to modify the property of the nanomedicines themselves in order to maximize their transport through cavitation-induced microstreaming. A new type of cavitation-inducing nanoparticle, known as ‘nanocups’, is developed that permits sustained cavitation activity throughout the tumour volume, significantly enhancing delivery and efficacy of last-generation anti-cancer agents. Further modification of these agents by applying a gold coating that increases their density is found to yield further enhancements in tumour penetration and delivery. These observations demand further mechanistic investigation of cavitation-induced microstreaming from a variety of agents including nanocups, nanodroplets and microbubbles and its impact on the transport of nanoparticles of different density, shape and charge.
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The 10th Complex Motion in Fluids 2020
Max Planck Gesellschaft
MCEC
Twente
Centre for Scientific Computing
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