Ultrasound-enhanced delivery of targeted echogenic liposomes in a novel ex vivo mouse aorta model

Abstract

The goal of this study was to determine whether targeted, Rhodamine-labeled echogenic liposomes (Rh-ELIP) containing nanobubbles could be delivered to the arterial wall, and whether 1 MHz continuous wave ultrasound would enhance this delivery profile. Aortae excised from apolipoprotein-E-deficient (n = 8) and wild-type (n = 8) mice were mounted in a pulsatile flow system through which Rh-ELIP were delivered in a stream of bovine serum albumin. Half the aortae from each group were treated with 1-MHz continuous wave ultrasound at 0.49 MPa peak-to-peak pressure, and half underwent sham exposure. Ultrasound parameters were chosen to promote stable cavitation and avoid inertial cavitation. A broadband hydrophone was used to monitor cavitation activity. After treatment, aortic sections were prepared for histology and analyzed by an individual blinded to treatment conditions. Delivery of Rh-ELIP to the vascular endothelium was observed, and subendothelial penetration of Rh-ELIP was present in five of five ultrasound-treated aortae and was absent in those not exposed to ultrasound. However, the degree of penetration in the ultrasoundexposed aortae was variable. There was no evidence of ultrasound-mediated tissue damage in any specimen. Ultrasound-enhanced delivery within the arterial wall was demonstrated in this novel model, which allows quantitative evaluation of therapeutic delivery.

Passive imaging with pulsed ultrasound insonations

“…However, others have demonstrated that ELIP can be used for localized ultrasound-mediated drug release 43 and delivery. 51 Passive cavitation imaging could be used in these contexts to obtain spatially resolved feedback during a treatment. Optimization of ultrasound insonation pulses based on cavitation emissions has been proposed as an important step in achieving desired bioeffects.…”

Liposomes in Diagnosis and Treatment of Cardiovascular Disorders

“…ultrasound-enhanced delivery of rhodaminelabeled echogenic liposomes (rh-eliP) within the arterial wall to detect atheroma was observed in an ex vivo mouse model. 48 subendothelial penetration of rh-eliP was present in all ultrasound-treated aortae and was absent in those not exposed to ultrasound. almer et al recently investigated a promising new candidate for improved visualization of atherosclerotic plaques.…”

Drug carriers for vascular drug delivery

“…Ultrasound parameters to enhance the delivery of therapeutic-loaded echogenic immunoliposomes into the arterial wall for the treatment of atherosclerosis were investigated in an ex vivo mouse aorta model. By using anti-ICAM-targeted echogenic liposomes and following the 1-MHz wave ultrasound, greater adherence of the targeted liposomes to vascular endothelium and greater passage across the vessel wall was shown (47). It was also previously observed that targeting liposomes to ICAM-1, VCAM-1, fibrin, fibrinogen, and TF, in addition to application of ultrasound waves, was able to produce the targeted enhancement in the vessel walls 5 min after intravenous administration of targeted liposomes.…”