iRGD靶向载药脂质体-微泡复合物的制备及其靶向性研究

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。

Preparation and targeting effect of iRGD modified liposome-microbubble complex

OBJECTIVE To prepare iRGD modified liposome-microbubble complex and evaluate its targeting efficiency. METHODS Biotinylated iRGD liposomes (iRGD-lipo) and biotinylated ultrasound microbubbles (MBs) were prepared by film-ultrasonic dispersion method and combined by biotin-avidin-system. Targeting effect in vitro was determined with adhesion efficacy experiments. Targeting effect in vivo was determined by fluorescence intensity of drugs in tumor. RESULTS Average particle size and zeta potential of iRGD-lipo were (165.07±4.01) nm and (-12.92±0.26) mv, respectively, and drug loading of complex was (46.22±1.95) μg/10⁸. Adhesion efficacy experiments showed that quantity of microbubbles in targeted group was obviously larger than in control group (7.8±1.1, 0.2±0.45, P<0.01). Accumulation of IR-780 in tumors of targeted group was higher than that of control group as determined by visualized fluorescence of in vivo imaging. CONCLUSION iRGD modified liposome-microbubble complex (iRGD-lipo-MBs), as a targeted drug delivery system, can integrate ultrasound molecular imaging and ultrasound-triggered therapeutic drug delivery to increase accumulation of drugs in tumors.