Ultrasound stimulated release of liposomal calcein

Abstract

Ultrasound exposure parameters that maximize drug release from liposomes were studied using two ultrasound transducers (300 kHz and 1 MHz). Variations in acoustic peak negative pressure (260-2037 kPa), temporary average intensity (0.05 6.08 W/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ), mechanical index (MI) (0.4-3.0), insonation time (0.5-20 minutes), pulse repetition frequency (PRF) (100-1000 Hz) and pulse length (0.05-0.4 ms) were studied. Drug release was more efficient at 300 kHz compared to 1 MHz. A certain threshold in peak negative pressure had to be overcome to obtain drug release, and the pressure needed was lower at 300 kHz (0.72 MPa) than at 1 MHz (1.39 MPa) which corresponds to MI values of 1.30 and 1.39 respectively. Above the threshold the release increased with increasing temporal average intensity, peak negative pressure, MI and duty cycle (i.e PRF and pulse length). The release was found to increase with exposure time, where the profile followed a first-order kinetics. The first-order rate constant for the release increased linearly with MI. This indicates that the release of the drug from liposomes was caused by mechanical rather than thermal effects. The results demonstrate that ultrasound has a potential in enhancing drug release from liposomes and can potentially improve cancer therapy.