Acoustic radiation force enhances targeted delivery of ultrasound contrast microbubbles: In vitro verification
Acoustic radiation force enhances targeted delivery of ultrasound contrast microbubbles: In vitro verification
复制标题
DOI：
10.1109/tuffc.2005.1417264
复制
发表时间：
2005-03-01
影响因子：
3.6
通讯作者：
Hossack, JA
中科院分区：
文献类型：
--
作者：
Rychak, JJ;Klibanov, AL;Hossack, JA
最近的研究表明，靶向超声造影微泡可以实现对血管内病理区域的特异性粘附，但不能在高流量区域实现特异性粘附。有人建议可以使用声辐射来迫使自由流动的微泡流向目标，但这尚未得到实际目标造影剂的验证。我们提出的证据表明，声辐射确实增加了微泡的特定目标积累。将带有作为靶向配体的抗体的脂质微泡通过涂有作为靶蛋白的P-选择素的微毛细管流动室注入。垂直于流动方向施加 2.0 MHz 超声波脉冲。方向。在与换能器相对的流动室表面上观察到微泡积聚。在0.25 X 10(6) 至75 X 10(6) ml(-1) 的微泡浓度范围内，122 kPa 的声压可将微泡粘附增强高达60 倍。在临床剂量范围内的浓度下，声压介导最大的粘附增强。在 1244 s(-1) 的壁剪切速率下，声压增强目标接近 80 倍，表明该机制适合在高流量容器中实现目标微泡输送。在 25 至 122 kPa 之间，微泡粘附力随着声压的平方而增加，并且在较高压力下显着下降。
Recent research has shown that targeted ultrasound contrast microbubbles achieve specific adhesion to regions of intravascular pathology, but not in areas of high flow. It has been suggested that acoustic radiation can be used to force free-stream microbubbles toward the target, but this has not been verified for actual targeted contrast agents. We present evidence that acoustic radiation indeed increases the specific targeted accumulation of microbubbles. Lipid microbubbles bearing an antibody as a targeting ligand were infused through a microcapillary flow chamber coated with P-selectin as the target protein. A 2.0 MHz ultrasonic pulse was applied perpendicular to the flow. direction. Microbubble accumulation was observed on the flow chamber surface opposite the transducer. An acoustic pressure of 122 kPa enhanced microbubble adhesion up to 60-fold in a microbubble concentration range of 0.25 X 10(6) to 75 X 10(6) ml(-1). Acoustic pressure mediated the greatest adhesion enhancement at concentrations within the clinical dosing range. Acoustic pressure enhanced targeting nearly 80-fold at a wall shear rate of 1244 s(-1), suggesting that this mechanism is appropriate for achieving targeted microbubble delivery in high-flow vessels. Microbubble adhesion increased with the square of acoustic pressure between 25 and 122 kPa, and decreased substantially at higher pressures.