Abstract
Optimal ultrasound parameters to enhance delivery of therapeutic-loaded echogenic immunoliposomes (ELIP) into the arterial wall are 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. 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.
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