羧甲基壳聚糖超小超顺磁氧化铁纳米粒在大鼠体内的药动学特点及组织分布

范彩霞; 陈志喜; 高文慧; 赖水招; 郑锦坤

引用本文:	范彩霞,陈志喜,高文慧,赖水招,郑锦坤.羧甲基壳聚糖超小超顺磁氧化铁纳米粒在大鼠体内的药动学特点及组织分布[J].中国现代应用药学,2013,30(10):1088-1094.
	FAN Caixia,CHEN Zhixi,GAO Wenhui,LAI Shuizhao,ZHENG Jinkun.Pharmacokinetics, Tissue Distribution of O-Carboxymethyl Chitosans Ultrasmall Superparamagnetic Iron Oxide Nanoparticles in Rats[J].Chin J Mod Appl Pharm(中国现代应用药学),2013,30(10):1088-1094.

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羧甲基壳聚糖超小超顺磁氧化铁纳米粒在大鼠体内的药动学特点及组织分布
范彩霞¹, 陈志喜¹, 高文慧², 赖水招¹, 郑锦坤¹
1.汕头大学附属粤北人民医院，广东韶关 512026;2.广州医学院附属肿瘤医院，广州 510005

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，t_1/2，CL，V₂，差异显著(P<0.05)，且OCMCS-USPIO-NPs组t_1/2>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。

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

DOI：

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基金项目: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)

Pharmacokinetics, Tissue Distribution of O-Carboxymethyl Chitosans Ultrasmall Superparamagnetic Iron Oxide Nanoparticles in Rats

FAN Caixia¹, CHEN Zhixi¹, GAO Wenhui², LAI Shuizhao¹, ZHENG Jinkun¹

1.Affiliated Yuebei People’s Hospital, Shantou University, Medical College, Shaoguan 512026, China;2.Affiliated Cancer Hospital of Guangzhou Medical College, Guangzhou 510005, China

Abstract:

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, t_1/2, CL, V₂(P<0.05), the t_1/2 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.

Key words: ultrasmall superparamagnetic iron oxide nanoparticles atomic absorption spectroscopy pharmacokinetics tissue distribution