载10-羟基喜树碱脂质超声微泡在小鼠体内的药代动力学研究  

Study on Pharmacokinetics of Lipid Microbubble Loaded by 10-Hydroxycamptothecin in Mice

作　　者：严思静[1] 李攀[1] 任建丽[1] 袁佩[1] 王志刚[1] 

机构地区：[1]重庆医科大学超声影像学研究所,重庆医科大学附属二院超声科,重庆市400010

出　　处：《中国超声医学杂志》2009年第8期721-724,共4页Chinese Journal of Ultrasound in Medicine

基　　金：863项目（No2006AA02Z4FO）; 国家自然科学基金重点项目（No30430230）

摘　　要：目的制备载10-羟基喜树碱（HCPT）脂质超声微泡,检测其形态、粒径、电位,并探讨其在小鼠体内的药代动力学特征及在超声辐照下药物在小鼠肝脏的定位释放情况。 方法用机械振荡法制备载HCPT脂质超声微泡,在光学显微镜下观察其外观和分布情况,以马尔文激光粒径测量仪测量其粒径大小和Zeta电位;测定HCPT注射液、载HCPT脂质超声微泡（HLM）在不同时间点小鼠血浆中的药物浓度,数据用3P97药动学程序处理,得到各主要药代动力学参数;将实验小鼠分为HLM组、HLM辐照组、HCPT注射液组、HCPT注射液辐照组4组,分别注射HLM及HCPT注射液后,用一定声强的超声经体表定点辐照,用HPLC-荧光法测定小鼠肝脏中的HCPT含量。 结果光镜下观察载HCPT脂质超声微泡呈球形,粒径范围为（1.1±0.2）μm,平均粒径1.1μm,Zeta电位为-（3.9±0.8）mV;HLM及HCPT注射液的药-时曲线符合二室模型,HLM在多数取样时间点的血药浓度较HCPT注射液高,HLM在血浆中的消除半衰期（6.70h）较HCPT注射液（1.12h）明显提高,延长了药物在血浆中的滞留时间,同时提高了HCPT的生物利用度,其AUC（药-时曲线下面积）为HCPT注射液的5.5倍;HLM辐照组小鼠肝组织中的HCPT含量明显高于其余各组。 结论载HCPT脂质超声微泡粒径分布均一,可延长HCPT在体内的循环时间,在一定声强的超声定位辐照下能明显提高靶组织内的药物浓度。Objective To prepare the lipid ultrasound microbubble loaded by HCPT（HLM） and checkits appearance,mean diameter range,zeta potential.To explore the pharmacokinetics in plasma and the HCPT concentrations in liver after HLM was destructed by ultrasound.Methods The HLM was prepared by mechanical vibration.The light microscope was used to evaluate its appearance,the malvern laser particle size measuring instrument was used to evaluate its mean diameter range and the zeta potential.In pharmacokinetics study,HCPT concentrations in plasma of the mice at different time points were processed by 3P97 program.After the mice were divided into 4 groups （HLM,HLM with ultrasound,HCPT injection,HCPT injection with ultrasound）,the HCPT injection and HLM were intravenously injected into the mice respectively and destructed by ultrasound from its body surface,then the concentrations of HCPT in liver were determined by HPLC-fluorometric method.Results The light microscope imaging showed that the HLM exhibited a spherical shape,the mean diameter range of which was （1.1±0.2）μm.The mean diameter was 1.1μm.Zeta potential was -（3.9±0.8）mV.The concentration-time curve of HLM and HCPT injection were in accordance with a two-compartment model.HCPT plasma concentrations of HLM were higher than those of HCPT injection at almost all sampling time.It also showed longer elimination period （6.70 h） than the HCPT injection （1.12 h）.Its circulation period was prolonged and bioavailability of HCPT was increased.Its AUC was 5.5 times of that of HCPT injection.After HLM and HCPT injection were destructed by ultrasound from body surface of mice,the concentrations of HCPT in liver in the HLM group were the highest among the groups.Conclusions The HLM can prolong circulation period in mice and promote the blood drug level obviously in target tissue after destructed by a certain ultrasound energy from body surface.

关 键 词：造影剂 10-羟基喜树碱 药代动力学 血药浓度 

分 类 号：R737.14[医药卫生—肿瘤] R971.9[医药卫生—临床医学]