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

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。

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

AIM:To study the distribution characteristics and liver targeting trend of adriamycin-loaded chitosan nanoparticles surfacemodified with glycyrrhizin(GL-ADM-NPs)in mice.METHODS:The GL-ADM-NPs,adriamycin-loaded chitosan nanoparticles (ADMNPs),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 targering 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 Re and Ce 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 43.06%and 62.58%of the values of F-ADM.CONCLUSION:GL-ADM-NPs changes the tissue distribution of ADM,has the liver targeting effect,and might decrease the side effects of ADM.It will be a promising carrier to deliver ADM to liver.