Ultrasound (US) can initiate the release of drugs from liposomes via an event called inertial cavitation, whereby the rarefactional phase of an ultrasound wave causes the expansion of a gas bubble followed by a violent collapse due to the inertia of the surrounding media. This collapse creates shock waves which can disrupt the stability of co-localised liposomal drug carriers. To date, studies have concentrated on the use of low frequency or high intensity US to generate gas bubbles in situ, and most recently such parameters have been used to achieve a variable level of triggered drug release following an intratumoral injection of liposomes [14]. However, concerns persist over the damage to non-target tissue that such US exposure parameters may cause and whether ultimately they will be widely clinically applicable. An alternative strategy is to utilise high-frequency US pulses at pressures in the diagnostic range in the presence of pre-existing gas bubbles. This provides an inertial cavitation stimulus for drug release using safe, clinically achievable US exposure conditions and approved US contrast agents [15]. Indeed, in the context of improving the delivery of therapeutics such as oncolytic viruses, this approach has already shown great promise [16]. A further advantage of this approach is that US-induced cavitation events produce distinct acoustic emissions that can be recorded and characterised providing non-invasive feedback, a feature which has proven useful in ablative US applications [17–19].
