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目的:制备iRGD靶向载药脂质体-微泡复合物,研究其靶向性。方法:采用薄膜-超声分散法制备生物素化的iRGD靶向载药脂质体和生物素化的超声微泡。利用生物素-亲和素系统(Biotin-avidin-system,BAS)连接脂质体与微泡,构建并表征iRGD靶向载药脂质体-微泡复合物。细胞黏附实验验证复合物的体外靶向结合性能;构建小鼠乳腺癌移植瘤模型,通过靶组织的药物荧光强度验证复合物的体内靶向性。结果:iRGD靶向载药脂质体的粒径为(165.07±4.01)nm,电位为(-12.92±0.26)mv,复合物的载药量为每108个复合物载紫杉醇(46.22±1.95)μg;黏附实验表明靶向组复合物与血管内皮细胞结合数量明显多于非靶向组复合物(7.8±1.1,0.2±0.45,P<0.01);荷瘤小鼠活体成像实验显示靶向组复合物的肿瘤组织荧光明显强于非靶向组复合物。结论:iRGD靶向载药脂质体-微泡复合物,作为一种靶向给药系统,可以实现超声分子成像与超声给药的有机结合,显著提高药物靶向递送的效率。
OBJECTIVE: To prepare iRGD targeted drug-loaded liposome-microbubble complexes and study their targeting. Methods: Biotinylated iRGD targeting drug-loaded liposomes and biotinylated ultrasound microbubbles were prepared by membrane-ultrasonic dispersion. Liposomes and microbubbles were ligated with Biotin-avidin-system (BAS) to construct and characterize iRGD targeted drug-loaded liposome-microbubble complexes. Cell adhesion assay was used to verify the in vitro binding activity of the complex. The mouse breast cancer xenograft model was constructed, and the in vivo targeting of the complex was verified by the fluorescence intensity of the target tissue. Results: The particle size of iRGD targeting drug-loaded liposomes was (165.07 ± 4.01) nm and the potential was (-12.92 ± 0.26) mv. The drug loading of iRGD was 46.22 ± 1.95 per 108 complexes, μg / ml. Adhesion experiments showed that the number of complexes of target group and vascular endothelial cells was significantly higher than that of non-target group (7.8 ± 1.1,0.2 ± 0.45, P <0.01). Live imaging experiments in tumor-bearing mice showed that target group Complex tumor tissue fluorescence was significantly stronger than non-target group complexes. CONCLUSIONS: iRGD is targeted to drug-loaded liposome-microbubble complexes. As a targeted drug delivery system, iRGD can achieve the organic combination of ultrasound molecular imaging and ultrasonic administration, and significantly improve the efficiency of targeted drug delivery.