载药脂质微气泡的制备及其应用

Preparation of acoustically active lipospheres containing paclitaxel

目的制备载紫杉醇脂质微气泡并测定其包封率、载药量、药物释放及观察其体内超声显像效果。方法制备载紫杉醇脂质微气泡，测定其包封率，载药量，粒径大小、分布和Zeta电位；观察苏丹黑对脂质微气泡的染色，以及超声辐照后苏丹黑的释放情况；观察辐照后载药脂质微气泡各层溶液药物的释放；并观察其在小鼠肝内的显像效果。结果载药脂质微气泡的浓度为2．3×10^9～3．5×10^9／ml，粒径范围为90％以上2～6μm，平均粒径为2．95μm。脂质微气泡紫杉醇的包封率大于90％，载药量为（26．5±0．7）％；Zeta电位为-（21．8±1．1）mV；苏丹黑染色后光镜下可见微气泡壁被染成黑色，超声辐照后微气泡稀释液变黑，并且超声辐照载药脂质微泡溶液后，上层和中间层的药物释放明显增加；静脉注射此载药微气泡后，小鼠肝可见良好、持续的增强显像效果。结论采用机械振荡法制备的紫杉醇脂质微气泡，包封率和载药显均较高，粒径分布好，体内显像效果好，超声辐照能促使微泡中的药物释放，有望实现实时监控下的体内定点靶向给药。

Objective Self-made paclitaxel-carrying lipospheres were developed and evaluated as a new ultrasound contrast agent for chemotherapeutic drug delivery. Methods Paclitaxel was added to an aqueous suspension of phospholipids in vial. The headspace of the vials was replace with perfluorobutane gas;the vials were sealed,and they were agitated 30 s on a shaking device. The resulting lipospheres containing paclitaxel were studied for concentration, size, drug entrapment efficiency, drug-loading amounts. Drug release with ultrasound was observed. Results Acoustically active lipospheres containing palitaxel had a mean partical count of approximately 2.3 × 10^9-3.5 × 10^9/ml and a mean size of 2.95μm. The drug entrapment efficiency was more than 90% and the drug-loading amounts was （26.5 ± 0.7）%. The paclitaxel-carrying lipospheres reflect ultrasound as a contrast agent. Fixing amounts of ultrasound energy ruptured the microbubble and released the paclitaxel. The liver imaging of the mice could be enhanced obviously and persistently. Conclusions Liposome microbubbles represent a new class of acoustically active drug delivery vehicles. Future studies will assess efficacy of self-made microbubbles for ultrasound-mediated drug delivery.