Relationship between cavitation, rapid loss of echogenicity, and drug release from echogenic liposomes.

Abstract

Echogenic liposomes (ELIPs), encapsulating air and drug, are being developed for use as vesicles for ultrasound-mediated drug release. Both calcein and a thrombolytic drug have been encapsulated in ELIP and released with 6-MHz color Doppler ultrasound in an in vitro flow system. To elucidate the role of stable or inertial cavitation in loss of echogenicity and drug release, ELIPs were insonified with 6-MHz pulsed Doppler ultrasound within the same flow system. A 10-MHz focused passive cavitation detector (PCD) was placed confocally with the pulsed Doppler sample volume. B-mode images and PCD signals were recorded during ELIP infusion (5 ml/min) and exposed to pulsed Doppler over a range of peak rarefactional pressure amplitudes (0–1.4 MPa) at two pulse repetition frequencies (1250 and 2500 Hz). The mean digital intensities were calculated on each image within two regions of interest placed upstream and downstream of the Doppler sample volume. The thresholds for rapid loss of echogenicity were ascertained from six B-mode images acquired over 30 s. These thresholds were compared to stable and inertial cavitation thresholds. The implications of these data on the mechanism of rapid liberation of gas and drug release will be discussed. [Work supported by the NIH R01 HL059586 and NIH R01 HL7400]