Increasing the Endothelial Layer Permeability Through Ultrasound-Activated Microbubbles

Drug delivery to a diseased tissue will be more efficient if the vascular endothelial permeability is increased. Recent studies have shown 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 in the absence of cell damage. To investigate the feasibility of controlled increased endothelial layer permeability, we treated monolayers of human umbilical vein endothelial cells with ultrasound and the contrast agent BR14. Barrier function was assessed by measuring transendothelial electrical resistance (TEER). Ultrasound-activated BR14 significantly decreased TEER by 40.3%$\,\pm\,$3.7% ( $p ≪ 0.01$). After treatment, no cell detachment or damage was observed. In conclusion, ultrasound-activated BR14 microbubbles increased the endothelial layer permeability. This feature can be used for future ultrasound-guided drug delivery systems.