【摘要】 目的制备性能稳定的亚微米级紫杉醇微泡超声造影剂,观察脉冲式超声激励下其在肿瘤局部的释放。方法用三醋酸甘油酯溶解紫杉醇,加入脂质冻干粉,制成亚微米级的载紫杉醇超声微泡,对其进行形态学及质量检测。建立兔VX2乳腺癌模型,将24只模型兔随机分成4组,经耳缘静脉注射紫杉醇微泡或紫杉醇后,采用或不用脉冲超声于体表定点辐照,10 min后即刻剖取瘤块,用反相高效液相色谱法检测肿瘤组织中的紫杉醇含量。结果载紫杉醇脂膜微泡的粒径为299.8~2383.5 nm,平均(1.07±0.38)μm,浓度9×109~10×109/ml,表面电位为(19.10±0.32)mV,包封率为(95.00±1.22)%,载药量(5.60±0.11)%。超声释放实验显示紫杉醇微泡加超声辐照组肿瘤组织内的紫杉醇含量明显高于其他各组的药物含量(P<0.05)。结论在低能量超声激励下,亚微米级紫杉醇载药微泡能实现在肿瘤局部高浓度释放紫杉醇,增强疗效并减少全身不良反应。更多还原

【Abstract】 Objective To prepare a submicro-scale paclitaxel-loaded lipid microbubbles(PLM),and to observe the release to regional tumor under pulsed ultrasound excitation.Methods Paclitaxel-loaded lipids were prepared with lyopyilization and mixed triacetin-dissolved paclitaxel.Then the microbbubles were made using mechanical excitation.The shape and quality of PLM were examined.Twenty-four rabbit models of VX2 breast carcinoma were established by means of injection of tissue mass suspension and were divided into 4 groups.Tumor was removed after plus or no ultrasound irradiation 10 min after injected PLM or paclitaxel in vein.Concentration of paclitaxel in VX2 breast tumor location in rabbit was compared with RP-HPLC in 4groups.Results Particle size range of PLM was 299.8—2383.5 nm,mean bubble diameter was(1.07±0.38)μm,concentration was 9×109—10×109/ml,the surface potencial was(19.10±0.32)mV,entrapment efficiency was(95.00±1.22)% and drug-loading was(5.60±0.11)%.The contents of paclitaxel in tumor tissues was higher in PLM associated with ultrasound excitation group(P<0.05).Conclusion Excitated by lower energy ultrasound,PLMs enable release of druggery in high concentration in regional tumor and enhance the therapy effect and reduce side effect.更多还原