不同粒径的介孔纳米硅材料对小鼠的急性毒性研究  

Acute toxic effects of different-size mesoporous silica nanoparticles on mice by intravenous injection

作　　者：席晨[1] 王周华[1] 梁金强[1] 黄芝瑛[1] 

机构地区：[1]中山大学药学院,广东广州510006

出　　处：《中国药理学通报》2013年第10期1444-1448,共5页Chinese Pharmacological Bulletin

基　　金：科技部"十一五"国家科技支撑计划重点项目(No2008BAI55B03)

摘　　要：目的介孔二氧化硅纳米粒（mesoporoussilicananoparticles，MSN）是一种新型、潜在的药物纳米载体。为探索其可能存在的毒性，本研究采用小鼠进行急性毒性研究，分析毒性与材料粒径的关系。方法使用上下法主试验，经静脉注射途径将3种不同粒径（80、200、1000nm）及二氧化硅粉（20nm）分别给予小鼠，观察动物的毒性反应，存活动物观察14d，计算半数致死量（LD50）。观察期结束后，取血进行血生化检测，并对其进行大体解剖，摘取心、肝、脾、肺、肾和大脑，称重并计算脏器系数，制片及进行病理组织学检查。结果MSNs对小鼠有明显的急性毒性，20、80、200、1000nm给予小鼠静脉注射的LD50范围分别为：（26．3～32．8）、（100～125）、（304．7～381）、（80～100）mg·kg^-1；即毒性大小为20nm〉1000nm〉80nm〉200nm。结论MSNs会对小鼠造成急性毒性，并且毒性强弱与其粒径密切相关。Aims To investigate the potential toxic effects of mesoporous silica nanoparticles （MSN） on mice by intravenous injection, and the relationship be- tween particle size and toxicity. Methods The Up and Down method was used to test the median lethal dose （LD50） of the three particle-size MSNs （80, 200, 1000 nm） and silica powder （20 nm） to mice, and the surviving mice were observed for 14 days, with calculation of median lethal dose （LD50）. At the end of observing period, mice were sacrificed after the blood sample was taken to be deteded biochemically, heart, liver, spleen, lung, kidney and brain were re- moved and weighed precisely, and the relative organ weight was calculated, followed by pathology examina- tion. Results MSNs caused a significant acute toxici- ty to mice, and the intravenous LD50 ranges of 20, 80, 200, 1000 nm were respectively： 26.3 -32. 8, 100 - 125, 304.7 -381,80 - 100mg ·kg^-1 , so the toxicity relationship was 20 nm 〉 1000 nm 〉 80 nm〉 200 nm. The primary toxicity target organs via i.v. might be spleen, liver and kidney. Conclusion MSNs would cause acute toxicity in mice, and the virulence is closely related to its size.

关 键 词：介孔二氧化硅纳米颗粒 粒径 小鼠 静脉注射 急性 毒性 半数致死量（LD50） 

分 类 号：R-332[医药卫生] R197.38