Validation of an acoustic cavitation dose with hydroxyl radical production generated by inertial cavitation in pulsed mode: Application to in vitro drug release from liposomes

The purpose of this study was to define and validate an inertial cavitation dose (CD) based on the detection of broadband noise, designed to monitor ultrasound-mediated drug release from liposomes. The validation consists of using the terephthalate dosimeter to quantify by fluorescence measurements the extent of hydroxyl radical (OH) production during inertial cavitation. Sonication of samples was performed using tone bursts (pulse repetition frequency (PRF): 10 Hz−1 kHz, duty cycle (dc): 5–25%, Isppa: 4100–12,200 W/cm2) generated by a 1 MHz focused transducer. Three sets of ultrasound parameters with different PRF and dc were selected to be more precisely compared. Results demonstrated an excellent correlation between OH radical production and CD for each set of parameters, but significant differences in hydroxyl radical levels were observed among the sets of parameters. The results were compared with other studies, and the same tendency of variation with pulse duration was demonstrated. Results also showed that the CD was not distorted by peak intensity variations and was a much more reliable indicator than sonication time. Consequently, one validated parameter was selected to monitor drug release from two liposome formulations, and compare their ultrasound sensitivity.