纳米级全氟丙烷脂质超声微泡造影剂的制备

Preparation of nanoscale ultrasound microbubbles contrast agent

目的研制一种新型的直径在纳米级的全氟丙烷脂质超声微泡造影剂，检测其物理特征，探讨并验证其最佳制备条件。方法以混合的半合成磷脂和全氟丙烷作基本原料，司盘60和吐温80为膜稳定剂，以高剪切分散法制备纳米级超声微泡造影剂。荧光显微镜观察形态分布特点，激光粒度分析仪检测其粒径分布。经均匀设计法及多元回归分析探索各制备条件对超声微泡粒径的影响。结果经多元回归分析得出高剪切速度和高剪切时间对超声微泡粒径有显著性影响，最优制备条件为：高剪切速度为6档；高剪切时间为8min；DPPC浓度20mg／50ml；T80／S60比值为1，该条件下制备的超声微泡分散均匀、浓度较高，平均粒径为（335±5）nm。结论最优条件高剪切分散法制备的超声微泡造影剂粒径分布在208～416nm之间，是一种达到纳米级的新型超声微泡造影剂。

Objective To prepare a novel nanoscale ultrasound microbubbles contrast agents,test the physical properties, and validate the optimal preparation conditions. Methods High shear dispersing system was used to prepare nano-scale ultrasonic microbubble contrast agents using mixtures of pynthetie- glycero-phosphoryl and fluorocarbon gas （ C3 F8 ） as materials, and mixtures of the surfactants （ Span 60 and Tween 80） to help membrane stabilization. Fluorescence microscope and laser particle size analyzer were applied to detect the form and diameter. Uniform Design and multiple regression analysis were adopted to analyze the influence of preparation conditions. Results Multiple regression analysis revealed that the rotation speed and time of high shear dispersing could significantly influence the diameter of the micro-buubles, and the optimal preparation conditions were as follows ：rotation speed （6 grade） ,rotation time （8 rain）, DPPC concentration （20 mg/50 ml）,ratio of T80/S60 （1）. The ultrasound microbubbles prepared under these conditions were evenly dispersed with average diameters of （335 ± 5 ） nm. Conclusion The diameter of ultrasound mierobubbles contrast agents prepared by high shear dispersing system under the optimal preparation conditions was within 208 to 416 nm.