摘要
目的考察羧甲基壳聚糖超小超顺磁氧化铁纳米粒(O-carboxymethyl chitosans ultrasmall superparamagnetic iron oxide nanoparticles,OCMCS-USPIO-NPs)在SD大鼠体内的药动学特征及组织分布,为其临床应用提供依据。方法 SD大鼠随机分为生理盐水组、OCMCS-USPIO-NPs组和葡聚糖超顺磁氧化铁纳米粒组(dextran-SPIO-NPs),原子分光光度法测定血浆和心、肝、脾、肺和肾等组织的铁含量,DAS药动学软件对血药浓度-时间数据处理,求得OCMCS-USPIO-NPs组和dextran-SPIO-NPs组在大鼠体内的主要药动学参数;绘制组织内铁含量-时间曲线结合普鲁士蓝染色,比较OCMCS-USPIO-NPs和Dextran-SPIO-NPs在大鼠体内组织分布特点。结果 OCMCS-USPIO-NPs组和dextran-SPIO-NPs组的主要药动学参数(AUC,MRT,t1/2,CL,V2,差异显著(P<0.05),且OCMCS-USPIO-NPs组t1/2>7 h;OCMCS-USPIO-NPs组在肝、脾和肺的组织分布浓度显著低于dextran-SPIO-NPs组。结论 OCMCS-USPIO-NPs能逃避网状内皮系统吞噬,具有长循环作用。
OBJECTIVE To study pharmacokinetics features and tissue distribution of OCMCS-USPIO-NPs in SD rats in vivo to provide evidence for their clinical use in future. METHODS SD rats were divided into three groups： blank group, OCMCMS-USPIO-NPs group and dextran-SPIO-NPs group, then iron content in plasma and different tissue including heart, liver, spleen, lung and kidney were determined by atomic absorption spectroscopy. The iron concentration-time in plasma and tissues was drawn. The plasma concentration-time data of iron were analyzed by DAS 2.1.1 statistical software and the main pharmacokinetics parameters was caculated. Statistics analysis combined with Prussian blue staining were used to demonstrate OCMCS-USPIO-NPs and dextran-SPIO-NPs tissue distribution difference in rats. RESULTS There was significant difference between OCMCS-USPIO-NPs group and dextran-SPIO-NPs group in the main pharmacokinetics parameters of iron, including AUC, MRT, tl/2, CL, V2（P〈0.05）, the tl/2 in OCMCS-USPIO-NPs group were longer than 7 h in high or low dose group. Compared with dextran-SPIO-NPs group, not only statistical analysis but also Prussian blue staining results indicated the iron content in liver, spleen and lung in OCMCS-USPIO-NPs group were significant lower than dextran-SPIO-NPs. CONCLUSION OCMCS-USPIO-NPs can escape the RES capture to gain longer-circulation time.
出处
《中国现代应用药学》
CAS
CSCD
2013年第10期1088-1094,共7页
Chinese Journal of Modern Applied Pharmacy
基金
广东省自然科学基金博士启动项目(S2011040003279)
韶关市科学计划项目[韶科(卫)2011-20]
韶关市卫生局项目(Y11029)
关键词
超小超顺磁氧化铁纳米粒
原子分光光度法
药动学
组织分布
ultrasmall superparamagnetic iron oxide nanoparticles
atomic absorption spectroscopy
pharmacokinetics
tissue distribution
