超声脂质微泡与聚乳酸-聚乙醇酸共聚物纳米微球复合体在小鼠肝脏的定位释放

Positioning release of the complex of ultrasound microbubbles and poly lactate glycollic acid nano microspheres in the liver of mice

目的探讨新型超声微泡[荧光标记的聚乳酸-聚乙醇酸共聚物(PLGA)纳米微球与超声脂质微泡共价结合复合体]在一定声强的超声定位辐照下,PLGA纳米微球在小鼠体内肝脏组织的定位释放情况。方法用机械振荡法制备超声脂质微泡,双乳化法制备荧光标记的PLGA纳米微球,碳二亚胺法制备新型超声微泡。将实验小鼠分为3组:PLGA纳米微球组(NP组)、超声脂质微泡混合PLGA组(MB+NP组)、新型超声微泡组(MB-NP组),均用一定声强的超声经体表定点辐照小鼠肝脏。以激光共聚焦扫描荧光显微镜定性观察小鼠肝组织中PLGA纳米微球的分布。以DFY微泡测量软件对肝组织中荧光标记的PLGA纳米微球进行计数分析。结果 MB-NP组中的超声微泡周围布满数量不等的纳米微球,呈花环状,且PLGA纳米微球数量明显高于其他组(P均<0.01),MB+NP组的数量高于NP组(P<0.05)。结论新型超声微泡能够明显提高靶组织区内的PLGA纳米微球浓度,从而使PLGA携带的药物更多释放于靶组织中。

Objective To investigate the positioning release of poly lactate glycollic acid（PLGA） nano microspheres of novel ultrasoud microbubble（fluorescent labeled nano microspheres covalent bond with ultrasound microbubbles） with the ultrasound in the liver of mice.Methods Ultrasound microbubbles were prepared by mechanical shaking,PLGA nano microspheres were prepared by using double emulsification methods,and the novel ultrasound microbubble were prepared by carbodiimide method.Thiry-three mice were divided into 3 groups,i.e.PLGA nano microspheres group（NP group）,mixing group（MB＋NP group） and novel ultrasoud microbubble group（MB-NP group）.The mice were all radiated by ultrasound on their surface.Laser scanning confocal microscope was used to observe the distribution of PLGA nano microspheres in liver of mice.DFY software was used to analyze the amount of PLGA nano microspheres.Results In MB-NP group,a number of small round PLGA nano microspheres gathered around microbubbles like a garland was found.The amount of PLGA nano microspheres in MB-NP group was significantly higher than that in the other groups（both P0.01）,while in MB＋NP group was higher than in NP group（P0.05）.Conclusion The novel ultrasound microbubbles can obviously improve the concentration of PLGA nano microspheres,so that more drugs that PLGA nano microspheres carried could be released in the target tissue.