叶酸-羧甲基壳聚糖-超小超顺磁氧化铁纳米粒在大、小鼠体内的药代动力学、组织分布及磁共振响应特征

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

叶酸-羧甲基壳聚糖-超小超顺磁氧化铁纳米粒(folic acid-O-carboxymethyl chitosans ultrasmall super-paramagnetic iron oxide nanoparticles,FA-OCMCS-USPIO-NPs)是一种新型分子靶向的核磁共振造影剂。本文考察了其在正常大鼠和小鼠体内的药代动力学及磁共振响应特征,探讨该造影剂在动物体内的分布规律,为其肿瘤靶向造影提供依据。尾静脉给予高、低浓度的纳米粒后,采用邻二氮菲法测定大鼠血浆及小鼠组织内的铁含量并绘制药时曲线,求得两组药代动力学参数t1/2均大于7 h。组织分布结果显示只有少部分的纳米粒被肝、脾吞噬,而心、肺、肾内几乎没有分布,并且纳米粒的吞噬不随剂量的增加而增加。核磁共振结果显示,给药后4 h纳米粒开始由肾脏排泄,24 h时肝、肾的信噪比(SNR)恢复到正常水平,肺部没有纳米粒的分布。可见,部分纳米粒逃避了肝、脾的吞噬,具有低毒性和较长的半衰期,为肿瘤靶向造影奠定了基础。

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.All of these indicated its use for tumor-targeting imaging.