姜黄素固体脂质纳米粒的制备及其大鼠体内药代动力学的.doc

PAGE 1 PAGE 12 姜黄素固体脂质纳米粒的制备及其大鼠体内药代动力学的研究 李娟1＊ 王广基2 魏赟1（1. 中国药科大学药剂学教研室；2. 药物代谢与药动学研究中心，南京 210009） 摘 要 目的 采用乳化超声法制备姜黄素固体脂质纳米粒，研究大鼠静脉注射后的体内药代动力学。方法 采用均匀设计优化纳米粒处方和工艺，通过光子关联光度法测定其粒径和粒子表面的Zeta电位，建立RP-HPLC法测定药物血浆中浓度。结果 纳米粒平均粒径为182.6±3.1nm，Zeta电位为-28.3±1.2mV，包封率为79.36 %±1.02 %；纳米粒在20%乙醇溶液和0.25%Tween-80溶液中的释放动力学分别符合Higuchi和零级方程；大鼠静脉注射纳米粒和普通注射剂后的AUC0-∞是普通注射剂的7.9倍，纳米粒的平均滞留时间（MRT）和t1/2均延长分别为 1.571±0.204 h和1.258±0.210 h。结论 固体脂质纳米粒可明显提高姜黄素的体内生物利用度，延长体内生物半衰期。 关键词：姜黄素；固体脂质纳米粒；均匀设计；体外释放；理化性质；药代动力学 Preparation of curcumin solid lipid nanoparticles and evaluation of its pharmacokinetics in rats LI Juan1*, WANG Guang-ji2 ,WEI Yun1, (1. Department of Pharmaceutics, 2. Center of Pharmacokinetics, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing,210009,China) ABSTRACT: OBJECTION To prepare curcumin solid lipid nanoparticles(CM-SLN) using emulsify-ultrasound method. The pharmacokinetics of CM-SLN, after intravenous (i.v.) administration to male Wistar rats were evaluated.METHODS The formulations of CM-SLN were optimized by uniform experimental design method, Particle size and charge measurements were made with Malvern Zetasizer.The morphology of CM-SLN were examined by transmission electron microscope. Drug release in vitro in 0.25% Tween-80 solution and 20% ethanol solution were also investigated. CM-SLN and the conventional injections in rats plasma were compared by high performance liquid chromatography (HPLC). RESULTS At optimized process conditions, curcumin loaded SLN showed spherical particles with a average size was 182.6±3.1nm ,with a polydispersity index of 0.216±1.2 and the Zeta potential was -28.3±1.2mv. The entrapment efficacy of CM-SLN was 79.36±1.02%. In 0.25% Tween-80 solution the drug release of CM-SLN in vitro fit zero-level equation well and in 20% ethanol solution fit Higichi 通讯作者简介：李 娟（1961），女，副教授，硕士生导师，从事药物新剂型和新制剂研究。 Tel：025 E-mail：lijuancpu@163.com equation well,respecti