Ultrasound-triggered drug delivery for cancer treatment using drug delivery systems: From theoretical considerations to practical applications.

Ultrasound-triggered drug delivery is now becoming a mature technology with first patients enrolling in clinical trials. Having a clear overview of the field is complicated as it mixes ultrasound physics and biological effects, particle formulation, and pharmacokinetics and biodistribution. The scope of this review is to move from basics to the latest developments of combined techniques using ultrasound for triggering drug release. Generalities on ultrasound are first given to better understand the parameters on which the clinician can operate to modulate the amount of delivered energy. Ultrasound effects on biological tissues such as thermal effects, mechanical effects and radiation forces are also presented. The second part of this review deals with the combination of ultrasound and drug delivery systems to enhance the efficacy of current cancer treatment. The in vivo behavior of drug delivery systems and how ultrasounds can be combined to improve treatment efficacy are detailed. The example of ThermoDox®, a new formulation of thermosensitive liposomes undergoing a phase III clinical trial, is particularly discussed on the basis of the available clinical data. Through the present article, researchers will be able to better grasp the different levels of complexity when designing an efficient formulation to be combined with ultrasound.