羟基喜树碱长循环纳米粒的药动学与组织分布研究  

Study on pharmacokinetics and tissue distribution of hydroxycamptothecine long-circulation nanoparticles

作　　者：蒋梦玥 王彦苏 杜妍旖 黄明月 李木生 刘晓芳 王婴 王岩 JIANG Mengyue;WANG Yansu;DU Yanyi;HUANG Mingyue;LI Musheng;LIU Xiaofang;WANG Ying;WANG Yan(School of Traditional Chinese Medicine Guangdong Pharmaceutical University Guangzhou 510006 China;School of Medicine and Chemistry Engineering Guangdong Pharmaceutical University Zhongshan528458 China)

机构地区：[1]广东药科大学中药学院,广东广州510006 [2]广东药科大学医药化工学院,广东中山528458

出　　处：《广东药科大学学报》2018年第3期265-270,共6页Journal of Guangdong Pharmaceutical University

基　　金：国家自然科学基金资助项目(81673608);广东省科技计划项目(2015A020211034;2014A020212685);广州市科技计划项目(201707010155);广东省大学生科技创新培养专项基金(Pdjh2017b0268)

摘　　要：目的研究羟基喜树碱(HCPT)长循环纳米粒的药动学和组织分布特征。方法采用尾静脉注射给药,不同时间段对大鼠进行眼眶取血,摘除小鼠内脏,以HCPT普通纳米粒及HCPT溶液作对照,分别测定HCPT长循环纳米粒在大鼠体内的药动学参数和在小鼠各组织中药物浓度的变化。结果 HCPT长循环纳米粒在大鼠的体内过程符合二室模型特征;羟基喜树碱HCPT长循环纳米粒在小鼠的肝脏中质量浓度最高(63.11μg/mL),而心脏中仅为1.01μg/mL,分布顺序为肝>肺>脾>肾>心。结论与HCPT普通纳米粒和HCPT溶液相比,HCPT长循环纳米粒可显著提高药物的生物利用度,延长体内的滞留时间,并能形成显著的肝靶向。Objective To study the pharmacokinetics and tissue distribution of hydroxycampylocine （HCPT） long-circulation nanoparticles. Methods After tail vein injection,the blood was collected from eye socket and the mice organs were removed. The concentration of HCPT was determined to calculate HCPT long circulating nanoparticles pharmacokinetic parameters of HCPT long circulating nanoparticles in rats with normal HCPT nanoparticles and HCPT solution as comparison groups respectively and changes of HCPT concentration in mice. Results The process in rats of HCPT long-circulation nanoparticles conformed to two-compartment model. The highest concentration of HCPT long-circulation nanoparticles was obtained with 63.11 μg/mL in liver,while the concentration in heart was only 1.01 μg/mL. The sequence of HCPT levels in different tissues was： liver〉lung〉 spleen〉kidney〉heart. Conclusion Compared with HCPT conventional nanoparticles and solution,HCPT long-circulation nanoparticles can significantly improve HCPT bioavailability,prolong its retention time in vivo and form significant liver targeting.

关 键 词：羟基喜树碱 长循环纳米粒 药动学 组织分布 

分 类 号：R965[医药卫生—药理学]