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

Abstract

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/cm(2)) 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.

Focused ultrasound influence on calcein-loaded thermosensitive stealth liposomes

“…Ultrasound-mediated mechanical stimulus has been reported to enhance the extravasation of free drug [11] and drug-loaded liposomes [12] from the tumour vascular compartment into tumour interstitial tissues. Moreover, mechanical stimuli, including inertial cavitation [13][14][15] and acoustic streaming [16], serve as external triggers for targeted drug release from nanoparticles. Recent investigations support the extended use of FUS for temperature-induced local drug delivery at mild hyperthermia (i.e.…”

In Vitro Investigation of the Individual Contributions of Ultrasound-Induced Stable and Inertial Cavitation in Targeted Drug Delivery

“…This is contradictory to the common assumption that UmTDD is governed by 378 inertial cavitation (Somaglino et al 2011;Razavi et al 2014). Here we have provided evidence that 379 stable cavitation with a lower CD, in the presence of MB, produces a greater impact on the 380 intracellular uptake.…”

Quantitative evaluation of hemolysis in bovine red blood cells caused by acoustic cavitation under pulsed ultrasound

“…These experimental results imply that the hemolysis is related to acoustic cavitation since the sound pressure threshold for cavitation generation increases with the ultrasound frequency. Acoustic cavitation increases the dose efficiency in ultrasound-triggered gene and drug delivery techniques [8], and the ultrasound pulse length is one of the important factors in cavitation generation and in determining the efficiency [9].…”

“…These experimental results imply that the hemolysis is related to acoustic cavitation since the sound pressure threshold for cavitation generation increases with the ultrasound frequency. Acoustic cavitation increases the dose efficiency in ultrasound-triggered gene and drug delivery techniques [8], and the ultrasound pulse length is one of the important factors in cavitation generation and in determining the efficiency [9].In this paper, we focused on hemolysis caused by pulsed ultrasound and performed in vitro experiments using bovine blood. Temporal changes in the generation of cavitation were measured while changing the pulse repetition frequency (PRF) and pulse length, and the relationship between the hemolysis and the acoustic cavitation was evaluated quantitatively.…”