1F-6 Transiently Increased Endothelial Layer Permeability by Ultrasound-activated Microbubbles

To enhance drug delivery to the extravascular tissue, a controlled, temporal and local increase in endothelial permeability is needed. Although recent studies have established that the permeability of single-cell membranes is increased by ultrasound in combination with contrast agents, it is not known whether this combination can also increase the permeability of an endothelial layer. To investigate endothelial layer permeability, we treated layers of human umbilical vein endothelial cells with ultrasound and the contrast agent BR14. Endothelial layer permeability was assessed by measuring the transendothelial electrical resistance (TEER) and permeability for fluorescein. Ultrasound in combination with BR14 significantly decreased TEER to 68.0 plusmn 3.1 % of initial values and temporally increased endothelial permeability for fluorescein by 38.1 plusmn 16.4 %. After treatment, no cell loss or damage was observed. In conclusion, ultrasound-activated BR14 microbubbles transiently increased the endothelial layer permeability. This feature may be used for future ultrasound-guided drug delivery systems