纳米液态氟碳脂质微球超声造影剂的制备及体外聚集实验研究

Preparation and in vitro aggregation of a novel ultrasound contrast agent,perfluorocarbon lipid nanoparticles

目的制备一种新型超声造影剂——纳米液态氟碳脂质微球造影剂,并研究其体外基本特性及聚集后增强超声显影性能。方法采用高压均质法制备纳米液态氟碳脂质微球超声造影剂,检测一般理化性质,再制备生物素化微球,以空白微球为对照组,分别在加入亲和素前后,观察体外聚集情况及超声显影效果,并用DFY超声图像定量分析统计软件计算、比较超声图像平均灰度值。结果所制备的液态氟碳脂质微球为外观呈乳白色的混悬液,镜下微球形态圆整,大小均一,性质稳定,粒径(171.9±91.0)nm;制备的生物素化微球在加入亲和素后聚集成团状,并可增强超声显影,经DFY软件分析,加入亲和素前后超声图像平均灰度值差异有统计学意义。结论成功制备出稳定的纳米液态氟碳脂质超声造影剂,并采用生物素亲和素法证明了该微球具有聚集后增强超声显影性能。

Objective To develop a novel nanoscale ultrasonic contrast agent, perfluorocarbon lipid nano-particles and to investigate its basic characteristics and capability to enhance ultrasound images when aggregated. Methods Perfluorocarbon lipid nanoparticles were prepared by lecithin and liquid perfluorocarbon with a high pressure homogen. The physieo-ehemical properties of the nanoparticles were detected. Strepavidin was added to the preparation procedure to produce biotinylated perfluorocarbon lipid nanopartieles. Blank nanoparticles with or without biotinylation served as control. The 4 kinds of nanoparticles were used for ultrasound imaging. The aggregation, contrast effect of these agents were studied, and the average gray scale value of the captured ultrasound images were analyzed by the DFY software. Results These nanoparticles were uniform and stable, and with a mean size of （171.9±91.0） nm. There was no visible ultrasound signals scattered with the nanoparticles before adding strepavidin, while obviously ultrasound echo signals were observed in those biotinylated nanoparticles, with significant difference between the ultrasound images before/after biotinylation. Conclusion A steady perfluorocarbon lipid nanoparticles are prepared, and can aggregate together in the existence of strepavidin and enhance the ultrasound image. The aggregated nanoparticles might be regarded as a ultrasound contrast agent.