新型液态氟碳纳米脂质微球超声造影剂的制备及显像实验研究

Experimental study on preparation and in vivo enhanced effect of a novel lipid perfluorooctylbromide nanoparticles

目的制备液态氟碳（perfluorooctylbromide，PFOB）纳米脂质微球并探讨其对大鼠肝脾实质的超声显像效果、安全性及相关机制。方法采用高压均质技术制备PFOB纳米脂质微球，用透射电镜观察微球形态、分布，用激光粒度和电位分析仪测定微球粒径及表面电位。经大鼠尾静脉注射微球后行超声显像，同时监测大鼠生命体征变化。肝脾实质为感兴趣区，应用DFY超声图像定量分析系统评价造影效果，建立时间一强度曲线。大鼠肝脾冰冻切片探讨微球增强肝脾超声显像的相关机制。结果PFOB微球为实心球形结构，粒径极小且分布均匀；造影后约10S肝实质回声增强，达峰时间约在注射微球后3～4min，持续增强约1h；脾实质较肝实质增强时间更长，效果更显著，第2d仍持续增强；实验过程中大鼠生命体征未见明显变化；微球在肝脾组织内大量分布聚集可能是其增强肝脾显影的机制之一。结论PFOB微球是一种安全有效的新型超声造影剂，有潜在的开发应用价值。

Objective To prepare a kind of new lipid perfluorooctylbromide（PFOB） nanoparticles and to explore its potential application as an ultrasound contrast agent. Methods Lipid PFOB nanoparticles were prepared by microfluidization techniques. The morphology and distribution were observed with optical microscope and transmission electron microscope. Particle size and electric potential were determined with Malvern laser light scattering analyzer. Twelve normal Wistar rats were performed directly contrast imaging after injection of PFOB nanoparticles via caudal vein. Vital signs of the rats were monitored during the whole study. And echogenic intensity of the liver was dynamically quantified through DFY ultrasound quantified analysis system. The mechanism of enhancement was studied by the frozen sections of rat＇s liver and spleen. Results The nanoparticles size and distribution were highly uniformed. Tb.e grey scale ultrasound imaging of the rat＇s liver and spleen were enhanced by PFOB nanoparticles. Ten seconds after PFOB nanoparticles injected,enhancement of liver began, the peak time was approximately 3 - 4 rain, the duration of contrast enhancement was nearly up to I h. The enhancement of spleen was more significant and the duration was much longer. No abnormal changes of the rat＇s vital signs appeared during the study. Frozen sections suggested that PFOB nanoparticles accumulated in the liver and spleen was the potential mechanism of enhancement. Conclusions This novel and safe lipid PFOB nanoparticles could make prolonged enhancement of rat＇s liver and spleen,which has a good potency for ultrasound application.