载多西紫杉醇脂质微泡超声造影剂的制备及其性质

目的 制备载多西紫杉醇脂质微泡并测定性质及观察其体内显像效果.方法 制备载多西紫杉醇脂质微泡,测定粒径、包封率等性质;观察60Co射线灭菌前后微泡性质的差异,观察超声辐照后载药微泡药物的释放,并观察其对兔VX2肝癌的显像效果.结果 载多西紫杉醇微泡的浓度为2.2×109～3.2×109个/ml;粒径分布范围为473.4～706.6 nm,平均粒径为623.1 nm;微泡的包封率为70%以上,载药量为(17.5±0.8)%;Zeta电位为-(3.1±0.9)mV;超声辐照微泡溶液后,药物可释放;静脉注射此微泡后,兔肝实质见良好、持续的增强显像,肝癌病灶可见明显的"快进快出"显影表现.结论 载多西紫杉醇脂质微泡包封率较高,性质较佳,体内显像效果好,提高了超声在肝癌等肿瘤诊断中的价值,超声辐照能促使微泡中的药物释放,有望在实时监控下体内定点靶向给药,实现对肿瘤的靶向治疗.

The preparation and properties of docetaxel-carrying lipid microbubble ultrasound contrast agent

Objective Self-made docetaxel-carrying microbubbles were developed and evaluated as a new ultrasound contrast agent for diagnosis and targeted-chemotherapeutic drug delivery.Methods Docetaxel was mixed with an aqueous suspension of phospholipids in vials,which were put into 40℃ water for 30 minutes,after cooling,gas in vials was replaced with perfluoropropane gas,then vials were agitated for 45 s on a shaking device.Properties were studied contained concentration,size,zeta potential,drug entrapment efficiency and drug-loading amount.Drug released with ultrasound and imaging for VX2 carcinoma in rabbits were observed.Results Docetaxel-carrying microbubbles had a concentration of approximately 2.2×109～3.2×109/ml,a mean size of 623.1 am and a zeta potential of -(3.1±0.9)mV.Size distribution was 473.4～706.6 nm.Drug entrapment efficiency was more than 70% and drug-loading amount was(17.5±0.8)%.Fixed amount of ultrasound energy ruptured microbubbles and released docetaxel.Liver imaging of rabbits could be enhanced obviously and persistently,"fast in and out"phenomena was typical of VX2 carcinoma.Conclusions Liposome microbubbles represent a new class of acoustically active drug delivery vehicles.Docetaxel-carrying microbubbles can promote the value of ultrasound in tumor diagnosis,and docetaxel-carrying microbubbles combined with ultrasound have a hope to establish a kind of real-time monitoring,targeted system for tumor therapy.