Price R J, Skyba D M, Kaul S, Skalak T C
Department of Biomedical Engineering and the Cardiovascular Division, University of Virginia, Charlottesville, VA, USA.
Circulation. 1998 Sep 29;98(13):1264-7. doi: 10.1161/01.cir.98.13.1264.
We have previously shown that the application of ultrasound to thin-shelled microbubbles flowing through small microvessels (<7 microm in diameter) produces vessel wall ruptures in vivo. Because many intravascular drug- and gene-delivery vehicles are limited by the endothelial barrier, we hypothesized that this phenomenon could be used to deliver drug-bearing vehicles to tissue.
An exteriorized rat spinotrapezius muscle preparation was used. Intravascular fluorescent red blood cells and polymer microspheres (PM) (205 and 503 nm in diameter) were delivered to the interstitium of rat skeletal muscle through microvessel ruptures created by insonifying microbubbles in vivo. On intravital microscopy, mean dispersion areas per rupture for red blood cells, 503-nm PM, and 205-nm PM were 14.5x10(3) microm2, 24. 2x10(3) microm2, and 27.2x10(3) microm2, respectively. PM dispersion areas were significantly larger than the mean dispersion area for red blood cells (P<0.05).
Microvessel ruptures caused by insonification of microbubbles in vivo may provide a minimally invasive means for delivering colloidal particles and engineered red blood cells across the endothelial lining of a targeted tissue region.
我们之前已经表明，对流经小微血管（直径<7微米）的薄壳微泡施加超声会在体内导致血管壁破裂。由于许多血管内药物和基因递送载体受到内皮屏障的限制，我们推测这种现象可用于将载药载体递送至组织。
使用大鼠斜方肌体外制备模型。通过体内对微泡进行超声照射产生微血管破裂，将血管内荧光红细胞和聚合物微球（PM）（直径分别为205和503纳米）递送至大鼠骨骼肌间质。在活体显微镜下，红细胞、503纳米PM和205纳米PM每次破裂的平均弥散面积分别为14.5×10³平方微米、24.2×10³平方微米和27.2×10³平方微米。PM的弥散面积显著大于红细胞的平均弥散面积（P<0.05）。
体内对微泡进行超声照射引起的微血管破裂可能为将胶体颗粒和工程化红细胞穿过目标组织区域的内皮内衬提供一种微创手段。
