比较嵌段共聚物微泡与脂质微泡造影剂的体外稳定性及体内超声造影效果

Stability in vitro and acoustic contrast-enhanced effect in vivo of block copolymer microbubbles:Comparison with lipid microbubbles

目的比较嵌段共聚物微泡造影剂与脂质微泡造影剂的体外稳定性及体内CEUS效果。方法采用单乳化法制备以mPEG-PLLA为外壳、包裹液态氟碳全氟戊烷的嵌段共聚物微泡造影剂,以机械振荡法制备脂质微泡造影剂,比较两种造影剂在体外随时间延长微泡数量的变化情况;经静脉团注造影剂进行新西兰大白兔肝脏造影,比较两种造影剂的始增时间、达峰时间、峰值强度、廓清时间等参数的差异。结果嵌段共聚物微泡造影剂稳定性明显高于脂质微泡造影剂,静置24h后微泡数量明显高于脂质微泡。兔肝CEUS结果显示,嵌段共聚物微泡造影与脂质微泡造影剂在低机械指数CEUS模式下均可明显增强,二者各项CEUS参数差异无统计学意义。结论嵌段共聚物微泡造影剂稳定性高于脂质微泡造影剂,用于兔体内CEUS可明显增强,可视为一种新型高分子微泡造影剂。

Objective To investigate the in vitro stability and in vivo acoustic contrast-enhanced effect of block copolymer microbubbles, and to compare them with those of lipid microbubbles. Methods The block copolymer microbubbles encapsulating perfluoropentane and lipid microbubbles were prepared by method of single emulsification and mechanical shaking, respectively, and the dynamical changes of microbubbles density were compared in vitro. After bolus intravenous injection, the contrast-enhanced start time, peak time, peak intensity and clearance time of rabbit livers were analyzed. Results Compared with lipid microbubbles, block copolymer microbubbles were more stable, and had higher density after standing for 24 h in vitro. The acoustic contrast-enhanced results showed that both block copolymer and lipid microbubbles enhanced obviously in rabbit livers under second harmonic imaging mode, and no significant differences of contrast-enhanced parameters were found. Conclusion The block copolymer microbubbles encapsulating perfluoropentane are more stable than lipid microbubbles in vitro, and enhance obviously under second harmonic imaging mode in vivo, which can be regarded as a novel macromolecule acoustic contrast agent.