甘草酸表面修饰阿霉素壳聚糖纳米粒在小鼠体内的组织分布

Tissue distribution of adriamycin-loaded chitosan nanoparticles surface-modified with glycyrrhizin in mice

目的:研究甘草酸表面修饰阿霉素壳聚糖纳米粒(GL-ADM-NPs)在小鼠体内的分布。方法:GL-ADM-NPs经小鼠尾静脉给药,采用液质联用(LC/MS/MS)法检测阿霉素在小鼠血浆、心、肝、脾、肺、肾中的浓度随时间的变化,并与游离阿霉素溶液(F-ADM)组和阿霉素壳聚糖纳米粒(ADM-NPs)组进行比较。以相对摄取率(Re)和峰浓度比(Ce)为指标评价其靶向性。结果:与F-ADM相比,ADM-NPs明显提高药物在肝脏中的浓度(Re和Ce分别为3.54和2.2);经甘草酸修饰后GL-ADM-NPs对肝脏的靶向作用更强,Re和Ce分别达到5.83和3.42,在心和肾中药物分布显著降低,AUC分别为F-ADM的43.06%和62.58%。结论:GL-ADM-NPs改变了药物ADM的体内分布特征,具有明显的肝靶向性,并能显著降低心和肾毒性,有望成为肝癌治疗药物ADM的理想输送载体。

AIM： To study the distribution characteristics and liver targeting trend of adriamycin- loaded chitosan nanoparticles surface- modified with glycyrrhizin （GL-ADM-NPs） in mice. METHODS： The GL- ADM-NPs, adriamycin-loaded chitosan nanoparticles （ ADM- NPs）, and free adriamycin solution （F-ADM） were intravenously administered to mice, respectively. The LC/MS/MS method was used to determine the concentrations of adriamycin in mice plasma, heart, liver, spleen, lung and kidney. The targeting efficiency was evaluated by targeting parameters （Re and Ce）. RESULTS： Compared with F-ADM, ADM-NPs obviously increased the adriamycin concentration in the liver, Re and Ce were 3.54 and 2.2, respectively. After modified with glycyrrhizin on the nanoparticle surface, GL-ADM-NPs showed a higher targeting efficiency in the liver. The Ro and Co were 5.83 and 3.42, respectively. The levels of GL-ADM-NPs in the heart and kidney tissues were significantly decreased. The AUC were 43.06o/oo and 62.58% of the values of F-ADM. CONCLUSION： GL-ADM-NPs changes the tissue distribution of ADM, has the effect, and mi ADM. It will ght decrease the liver side be a promising carrier targeting effects of to deliver ADM to liver.