The impact of microbubbles on measurement of drug release from echogenic liposomes

Abstract

Echogenic liposomes (ELIP) are under development to enable ultrasound-triggered drug delivery. The mechanisms of ultrasound-mediated drug release from ELIP are not well understood. The effect of cavitation activity on drug release from ELIP was investigated in flowing solutions using two fluorescent molecules: a lipophilic drug (rosiglitazone) and a hydrophilic drug substitute (calcein). ELIP samples were exposed to pulsed Doppler ultrasound from a clinical diagnostic ultrasound scanner at pressures above and below the inertial and stable cavitation thresholds. Control samples were exposed to Triton X-100, a detergent (positive control), or to flow alone (negative control). Fluorescence techniques were used to detect release. Encapsulated microbubbles reduced the measured fluorescence intensity. This effect should be considered when assessing drug release if microbubbles are present. Release of rosiglitazone or calcein compared to the negative control was only observed with detergent treatment, but not with ultrasound exposure, despite the presence of inertial or stable cavitation activity. Thus, cavitation activity did not correlate with release of rosiglitazone or calcein from ELIP using a clinical diagnostic ultrasound scanner. These findings lay the foundation for future studies of ultrasound-mediated drug delivery with ELIP.