0277: Ultrasound Mediated Drug Delivery

Abstract

Echogenic liposomes (ELIP) are under development to enable ultrasound-controlled drug delivery. Ultrasound-triggered release of hydrophilic and lipophilic agents from circulating ELIP in vitro using 6-MHz color Doppler ultrasound will be reviewed. The differential efficiency of ultrasound-mediated pharmaceutical release from ELIP for hydrophilic and lipophilic compounds suggests that hydrophilic drugs are better candidates for the design and development of ultrasound-controlled drug delivery systems. Optimal ultrasound parameters to enhance delivery of therapeutic-loaded ELIP into an artery are also being developed for the treatment of atherosclerosis. The aim of this work was to determine whether anti-ICAM-targeted, Rhodamine-labeled ELIP (Rh-ELIP) would adhere to and penetrate the vascular endothelium in atheromatous murine arterial segments with intravascular flow treated with 1-MHz continuous wave ultrasound (CW US). A broadband focused hydrophone, confocally aligned with the artery and 1-MHz transducer field was used as a passive cavitation detector (PCD). Arteries were insonified with 1-MHz CW US (0.49 MPa peak-to-peak pressure) and the PCD was used to verify the duration of the resulting stable cavitation. The perivascular saline was collected and analyzed spectrofluorometrically for the presence of Rh-ELIP. Arteries were prepared for histological analysis by a pathologist blinded to the exposure conditions. Arteries exposed to Rh-labeled ELIP and 1-MHz US exhibited greater adherence of Rh-ELIP to the vascular endothelium, and greater passage of Rh-ELIP across the vessel wall. No damage was detected in any of the arteries on histology. These studies will aid in the development of a strategy for improving atheroma treatment without causing ultrasound-related tissue damage. Echogenic liposomes (ELIP) are under development to enable ultrasound-controlled drug delivery. Ultrasound-triggered release of hydrophilic and lipophilic agents from circulating ELIP in vitro using 6-MHz color Doppler ultrasound will be reviewed. The differential efficiency of ultrasound-mediated pharmaceutical release from ELIP for hydrophilic and lipophilic compounds suggests that hydrophilic drugs are better candidates for the design and development of ultrasound-controlled drug delivery systems. Optimal ultrasound parameters to enhance delivery of therapeutic-loaded ELIP into an artery are also being developed for the treatment of atherosclerosis. The aim of this work was to determine whether anti-ICAM-targeted, Rhodamine-labeled ELIP (Rh-ELIP) would adhere to and penetrate the vascular endothelium in atheromatous murine arterial segments with intravascular flow treated with 1-MHz continuous wave ultrasound (CW US). A broadband focused hydrophone, confocally aligned with the artery and 1-MHz transducer field was used as a passive cavitation detector (PCD). Arteries were insonified with 1-MHz CW US (0.49 MPa peak-to-peak pressure) and the PCD was used to verify the duration of the resulting stable cavitation. The perivascular saline was collected and analyzed spectrofluorometrically for the presence of Rh-ELIP. Arteries were prepared for histological analysis by a pathologist blinded to the exposure conditions. Arteries exposed to Rh-labeled ELIP and 1-MHz US exhibited greater adherence of Rh-ELIP to the vascular endothelium, and greater passage of Rh-ELIP across the vessel wall. No damage was detected in any of the arteries on histology. These studies will aid in the development of a strategy for improving atheroma treatment without causing ultrasound-related tissue damage.