Ultrasound-mediated endothelial cell permeability changes with targeted contrast agents

The development of site-targeted ultrasound contrast agents (UCAs), gas-filled microbubbles conjugated with targeting ligands on their surface, has provided a novel means for the detection and evaluation of intravascular pathology, cellular imaging and for ultrasound-assisted drug and gene delivery. Endothelial monolayers form the main barrier for the passage of macromolecules and circulating cells from blood to the tissues and are immediately affected by any changes in inter-endothelial gaps. Targeted microbubbles in combination with low-frequency ultrasound may directly affect the endothelial cell membranes as to increase the permeability and thus aid in the absorption of drugs into tissues. In an effort to more rigorously quantify alterations in the endothelial barrier function ultrasound-mediated changes in endothelial cell permeability are examined in real-time using an Electric Cell Substrate Impedance Sensing (ECIS) device in conjunction with ultrasound and targeted contrast agents.