Comparing microbubble cavitation at 500 kHz and 70 kHz related to micellar drug delivery using ultrasound

We have previously reported that ultrasonic drug release at 70 kHz was found to correlate with the presence of subharmonic emissions. No evidence of drug release or of the subharmonic emissions were detected in experiments at 500 kHz. In an attempt to understand the difference in drug release behavior between low- and mid-frequency ultrasound, a mathematical model of a bubble oscillator was developed to explore the difference in the behavior of a single 10-μm bubble under 500- and 70-kHz ultrasound. The dynamics were found to be fundamentally different; the 500-kHz bubble follows a period-doubling route to chaos while a 70-kHz bubble follows an intermittent route to chaos. We propose that this type of “intermittent subharmonic” oscillation behavior is associated with the drug release observed experimentally.

► Bubble dynamics were compared at 500- and 70-kHz ultrasound. ► The dynamics were found to be fundamentally different. ► The 500-kHz bubble follows a period-doubling route to chaos. ► The 70-kHz bubble follows an intermittent route to chaos. ► Intermittent subharmonic oscillation behavior is related to acoustic drug release.