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叶酸 - O - 羧甲基壳聚糖超小超顺磁性氧化铁纳米粒子在小鼠和大鼠体内的药代动力学、组织分布及磁共振响应特性

[Pharmacokinetics, tissue distribution and magnetic resonance's response characterstics of folic acid-O-carboxymethyl chitosan ultrasmall superparamagnetic iron oxide nanoparticles in mice and rats].

作者信息

Gao Wen-Hui, Liu Shi-Ting, Fan Cai-Xia, Qi Lin-Yan, Chen Zhi-Liang

机构信息

Department of Pharmacy, Nanfang Hospital, Nanfang Medical University, Guangzhou 510515, China.

出版信息

Yao Xue Xue Bao. 2011 Jul;46(7):845-51.

PMID:22010356
Abstract

Folic acid-O-carboxymethyl chitosan ultrasmall superparamagnetic iron oxide nanoparticles (FA-OCMCS-USPIO-NPs) are a novel molecular targeting MR contrast agent. This paper reperts the pharmacokinetics and magnetic resonance response characteristics of FA-OCMCS-USPIO-NPs in normal rats and mice, and discussed its distributing regularity in animals, providing basis for tumor targeting imaging. O-phenanthroline method was used to determine iron content in rats' plasma and mice's organs following high and low doses of nanoparticles injected through tail vein, and the blood concentration-time curve was drawn, the calculated t1/2 of two groups were greater than 7 h. The results of tissue distribution showed that only a small part of nanoparticles were swallowed by the liver and spleen, while none in the heart, lung and kidney. At the same times, the phagocytosis of nanoparticles did not change with the dose. The results of MRI showed that renal excretion occurred 4 hours after injection, and signal to noise ratio (SNR) of liver and kidney returned to normal levels 24 hours after injection. There were no nanoparticles in the lungs. So a part of nanoparticles escaped from phagocytosis of liver and spleen, and it owned lower toxicity and longer half-life. indicated its use for tumor-targeting imaging. All of these indicated its use for tumor-targeting imaging.

摘要

叶酸 - O - 羧甲基壳聚糖超小超顺磁性氧化铁纳米粒子(FA - OCMCS - USPIO - NPs)是一种新型的分子靶向磁共振造影剂。本文报道了FA - OCMCS - USPIO - NPs在正常大鼠和小鼠体内的药代动力学及磁共振响应特性,并探讨了其在动物体内的分布规律,为肿瘤靶向成像提供依据。采用邻菲啰啉法测定经尾静脉注射高、低剂量纳米粒子后大鼠血浆及小鼠各脏器中的铁含量,绘制血药浓度 - 时间曲线,计算两组的t1/2均大于7小时。组织分布结果显示,纳米粒子仅少量被肝脏和脾脏摄取,心脏、肺和肾脏中未摄取。同时,纳米粒子的摄取量不随剂量变化。磁共振成像结果显示,注射后4小时出现肾脏排泄,注射后24小时肝脏和肾脏的信噪比恢复正常水平。肺部未发现纳米粒子。因此,一部分纳米粒子逃避了肝脏和脾脏的摄取,且毒性较低、半衰期较长,表明其可用于肿瘤靶向成像。所有这些都表明其可用于肿瘤靶向成像。

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