摘要
目的:制备具有肝细胞靶向的甘草酸表面修饰阿霉素壳聚糖纳米粒,并考察其理化特性。方法:采用离子凝胶法制备阿霉素壳聚糖纳米粒,再以高碘酸盐氧化法制备甘草酸表面修饰阿霉素壳聚糖纳米粒。激光透射电子显微镜观察纳米粒的形态,马尔文激光粒度仪测定其粒径。RP-HPLC法间接测定纳米粒中甘草酸结合率和阿霉素包封率,并初步研究体外甘草酸的结合稳定性和阿霉素释药特性。结果:电镜显示纳米粒呈类球形,平均粒径为179.5 nm,甘草酸结合率达到80%以上,在释放介质中,12 h的甘草酸结合率仍保持(65.2±3.4)%;纳米粒中阿霉素包封率达90%以上,体外释药缓慢,无明显的"突释"现象,72 h的累计释放百分率为(28±4.6)%。结论:本方法制备的甘草酸表面修饰阿霉素纳米粒工艺简单,包封率高,且甘草酸表面结合稳定,有望提高阿霉素的肝细胞靶向性。
Aim： To prepare and characterize the adriamycin-loaded chitosan nanoparticles of the surface-modified with glycyrrhizin （ GL-ADM-CS-NPs）. Methods： Adriamycin-loaded ehitosan nanoparticles （ADM-CS-NPs） were prepared by ionic gelation, then oxidized by sodium periodate and conjugated to surface free amino groups of ADM-CS-NPs. Transmission electron microscopy was used to assess the shape of the nanoparticles. Malvern Zeta Nano-ZS was applied to measure the particle size distribution. RP-HPLC was developed to determine GL-binding ratio and adriamycin （ADM） entrapment efficiency. In addition, GL-binding stability and ADM release characteristics were investigated. Results：The GL-ADM-CS-NPs were found spherical with an average diameter of 179.5 nm. The GL-binding ratio was at least 80% and was retained to be （65.2±3.4） % after 12 h-exposure to the release medium. The ADM entrapment efficiency was at least 90%. 72-h in vitro cumulative release of ADM from GL-ADM-CS-NPs was accounted by （28 ± 4.6） %. Turthermore, there was no apparant drug ＂burst release＂ in the process. Conclusion： GL-ADM-CS-NPs prepared with the simple method developed in this paper has the properties of high drug entrapment efficiency and high GL-binding stability, which might have the potential improving the hepatocellular targeting of ADM.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2007年第6期507-511,共5页
Journal of China Pharmaceutical University
基金
广东省自然科学基金资助项目(No.040100147)
关键词
阿霉素
壳聚糖纳米粒
甘草酸
表面修饰
adriamycin
chitosan nanoparticles
glycyrrhizin
surface-modification
