载紫杉醇的聚乳酸-卵磷脂纳米级微泡的制备及其在超声介导下对肝癌细胞生物效应的评价  

Paclitaxel loaded polylactidelecithin nanobubbles:Preparation and antitumor effect after ultrasoundmediated delivery

作　　者：葛建丽[1] 唐杰[2] 

机构地区：[1]濮阳市油田总医院超声科,河南省濮阳市457001 [2]中国人民解放军总医院超声医学科,北京市100853

出　　处：《世界华人消化杂志》2015年第13期2098-2103,共6页World Chinese Journal of Digestology

摘　　要：目的:本文旨在了解在超声介导下载药微泡对肝癌的治疗作用.方法:我们的研究中以聚乳酸(poly lactic acid,PLA)和卵磷脂为药物载体,以紫杉醇为模型药物,通过冷冻干燥技术以及改良的超声复乳-溶剂挥发法制备载紫杉醇的聚乳酸-卵磷脂纳米级微泡,考察主要的制备参数:(1)超声时间对载药微泡理化特性(包括:粒径、形态、载药量、包封率和超声介导下体外释药特性)的影响;(2)卵磷脂含量,优化其制备最佳条件;然后考察其对于人肝癌细胞的细胞毒性,及其在超声介导下对荷瘤小鼠的抑瘤率和治疗效果.结果:在制备初乳和复乳过程中我们发现在超声时间均为100 s、PLA与卵磷脂质量比为250∶50时可以制得较好的聚乳酸-卵磷脂纳米级微泡.其平均粒径为615 nm、内部为空心的纳米级微泡,药物包封率可达90.90%±5.79%,载药率可达到8.26%±0.53%,紫杉醇以无定型状态分布在微泡的壳内;其在体外药物释放具有零级释放、缓释以及在超声介导下加快药物释放的特点.并且在紫杉醇浓度为10μg/mL时HepG2人肝癌细胞的增殖率仅为43.37%±3.23%.结论:相对于单纯的紫杉醇注射剂而言,在超声介导下载药纳米级微泡注射剂可以提高抑瘤率并且还能减少对小鼠的不良反应.AIM： To prepare paclitaxel loaded polylactide- lecithin nanobubbles and assess their antitumor effect after ultrasound-mediated delivery. METHODS： Paclitaxel-loaded polylactide（PLA）-lecithin nano-scale bubbles were prepared using the modified ultrasonic double emulsion solvent evaporation technology （UDES）. The impact of preparing ultrasonic time and lecithin content on chemical and physical properties of drug-loaded microbubbles （including drug load, particle size, morphology, in vitro release characteristics and encapsulation efficiency） was assessed. Then, the inhibitory effect of the bubbles after ultrasound-mediated delivery on H22 tumors in mice derived from human hepatoma cells was evaluated. RESULTS, The obtained paclitaxel-loaded PLA- lecithin nano-scale bubbles had a relatively uniform size of around 615 nm, and the drug load rate was 8.26%. The drug entrapment efficiency could reach 90.90%. The drug was amorphously dispersed in the shell of the bubble. The in vitro drug release test showed zero-order release and retained release, which could be speeded up by ultrasound. HepG2 cell only had a proliferation rate of 43.37% ± 3.23% when the paclitaxel concentration was at 10 μg/mL.CONCLUSION： Ultrasound-mediated delivery of PLA-lecithin nanobubbles might have potential anticancer effects.

关 键 词：聚乳酸-卵磷脂 紫杉醇 纳米级微泡 超声造影剂 

分 类 号：R735.7[医药卫生—肿瘤]