DELIVERY OF COLLOIDAL, PARTICLES AND RED-BLOOD-CELLS TO TISSUE THROUGH MICROVESSEL RUPTURES CREATED BY TARGETED MICROBUBBLE DESTRUCTION WITH ULTRASOUND

Background-We have previously shown that the application of ultrasound to thin-shelled microbubbles flowing through small microvessels (<7 m u m in diameter) produces vessel wall ruptures in vivo. Because many i ntravascular drug- and gene-delivery vehicles are limited by the endot helial barrier, we hypothesized that this phenomenon could be used to deliver drug-bearing vehicles to tissue.Methods and Results-An exterio rized rat spinotrapezius muscle preparation was used. Intravascular fl uorescent red blood cells and polymer microspheres (PM) (205 and 503 n m in diameter) were delivered to the interstitium of rat skeletal musc le through microvessel ruptures created by insonifying microbubbles in vivo. On intravital microscopy, mean dispersion areas per rupture for red blood cells, 503-nm PM, suid 205-nn PM were 14.5 x 10(3) mu m(2), 24.2 x 10(3) mu m(2), and 27.2 x 10(3) mu m(2), respectively; PM disp ersion areas were significantly larger than the mean dispersion area f or red blood cells (P<0.05). Conclusions-Microvessel ruptures caused b y insonification of microbubbles in vivo may provide a minimally invas ive means for delivering colloidal particles and engineered red blood cells across the endothelial lining of a targeted tissue region.