载多西紫杉醇脂质微泡超声造影剂的制备及其性质

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

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2．2×10^9～3．2×10^9个／ml；粒径分布范围为473．4～706．6nm，平均粒径为623．1mm；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，有望在实时龄控下体内定点靶向给药，实现对肿瘤的靶向治疗。

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 × 10^9-3.2 × 10^9/ml, a mean size of 623.1nm and a zeta potential of - （3.1 ± 0.9）inV. 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.