Abstract
Vascular smooth muscle cells (VSMCs) are important targets in the treatment of atherosclerosis. However, the arterial media, where the majority of VSMCs reside, have proven to be a difficult target for drug/gene delivery. We have demonstrated that ultrasound enhances drug/gene delivery to VSMCs in vitro by using echogenic immunoliposomes (ELIPs) as the vector. This study aimed to evaluate whether ultrasound can similarly enhance the delivery of an agent to VSMCs, particularly within the arterial media, in vivo, using ELIP. Anti-smooth-muscle cell actin-conjugated calcein-loaded ELIP were injected into the peripheral arteries of Yucatan miniswine (n = 8 arterial pairs). The right-sided porcine arteries were treated with 1-MHz continuous-wave ultrasound at a peak-to-peak pressure amplitude of 0.23 +/- 0.05 MPa for 2 minutes. The contralateral arteries served as controls. Arteries were harvested after 30 minutes and imaged with fluorescence microscopy. Image data were converted to grayscale and analyzed by using computer-assisted videodensitometry. There was significant improvement in calcein uptake in all three arterial layers in the arteries exposed to ultrasound (> 300%). This enhanced uptake was site specific and appeared limited to the ultrasound-treated arterial segment. We have demonstrated enhanced delivery of a small molecule to VSMCs in all arterial wall layers, particularly the arterial media, using ultrasound and targeted ELIP. The combined effect of ultrasound exposure and ELIP as a contrast agent and a drug/gene-bearing vector has the potential for site-specific therapy directed at VSMC function.