The sonication of a tumor, where liposomes have been accumulated, allows potentially to release encapsulated drug and to promote its absorption in cells. Ultrasonic inertial cavitation is supposed to be implicated in the release of drug encapsulated in small solid liposomes under ultrasonic exposure. Inertial cavitation is strongly dependent on experimental conditions and can be very intense and unpredictable. The main objective of this thesis was to control and quantify inertial cavitation in order to induce drug release from liposomes. In this purpose, an inertial cavitation dose (CD), based on broadband noise emission associated with inertial cavitation, was defined to monitor in vitro encapsulated drug release. The CD was chemically validated with the dosing of hydroxyl radicals generated by bubbles collapses under various pulsed ultrasound exposures. A high correlation between doxorubicin (dox) release rate from liposomes and CD was de monstrated for all liposomes formulations tested and under different pulsed ultrasound exposures. The role of temperature on hydroxyl radical production and dox release was also investigated. The performed experiments allowed selecting the liposomes formulations that are the most sensible to ultrasound in order to test them on rats implanted with prostatic tumors. After several campaigns of in vivo experiments performed with various ultrasonic setups and liposomes formulations, the benefit of the combined treatment was demonstrated.
