Box-Behnken响应面法优化索拉非尼PLGA-TPGS聚合物纳米粒的处方与工艺
Optimization of the Prescription and Preparation Process of Sorafenib PLGA-TPGS Polymer Nanoparticles by Box-Behnken Response Surface Method
  
DOI:
中文关键词:  索拉非尼  PLGA-TPGS纳米粒  纳米沉淀法  Box-Behnken响应面设计法
英文关键词:Sorafenib  PLGA-TPGS nanoparticle  Nanoprecipitation method  Box-Behnken response surface method
基金项目:国家自然科学基金项目(81274099);安徽中医药大学研究生科技创新基金项目(2017YB10)
作者单位
黄宇哲,桂双英, 储晓琴 1.安徽中医药大学药学院安徽 合肥 2300122.安徽省中医药科学院药物制剂研究所安徽 合肥 230012 
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中文摘要:
      目的 优化索拉非尼聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]-维生素E-聚乙二醇1000琥珀酸酯(D-ɑ-tocopheryl polyethylene glycol 1000 succinate, TPGS)聚合物纳米粒的处方与制备工艺。方法 采用乳化-溶剂挥发法制备纳米粒,以包封率和载药量为评价指标,采用Box-Behnken响应面法考察索拉非尼与PLGA的质量比、有机相与水相的容积比、乳化剂维生素E-聚乙二醇1000琥珀酸酯(TPGS)的浓度因素对制备的影响,得到最优工艺参数,并对最优处方与工艺下纳米粒药物的体外释放、形态和粒径进行考察。 结果 最佳处方为:索拉非尼与PLGA的质量比为1∶11.56;有机相与水相的容积比为1∶5.56;乳化剂TPGS的浓度为0.03%。制备的优化纳米粒形态均一,平均粒径为249.6 nm,包封率为89.78%,载药量为9.41%。体外索拉非尼在含1%吐温-80的磷酸盐缓冲液(pH 5.0、pH 7.4)中呈二相释放,120 h累积释放率分别为80.69%±4.70%和40.67%±3.77%。结论 所优选的索拉非尼PLGA-TPGS纳米粒处方与工艺合理可行,体外实验具有明显的缓释作用,可为后期体内、体外研究提供实验基础。
英文摘要:
      Objective To optimize the prescription and preparation process of sorafenib PLGA-TPGS polymer nanoparticles. Methods Nanoparticles were prepared by the emulsion-solvent evaporation technique. With encapsulation efficiency and drug loading as assessment indices, the Box-Behnken response surface method was used to evaluate the influence of mass ratio of sorafenib to PLGA, volume ratio of organic phase to water phase, and concentration of the emulsifier vitamin E TPGS on preparation and to obtain the optimal processing parameters. The in vitro release, morphology, and particle size of the nanoparticles were observed under the optimal prescription and preparation process. Results The optimal prescription was a mass ratio of sorafenib to PLGA of 1∶11.56, a volume ratio of organic phase to water phase of 1∶5.56, and a concentration of TPGS of 0.03%. The optimized nanoparticles had uniform morphology, with an average particle size of 249.6 nm, an average encapsulation efficiency of 89.78%, and an average drug loading rate of 9.41%. In vitro sorafenib was released in two phases in 1% tween-80 phosphate buffer (pH 5.0 and pH 7.4), and the 120-hour cumulative release rates were 80.69%±4.70% and 40.67%±3.77%, respectively. Conclusion The optimized prescription and preparation process of sorafenib PLGA-TPGS polymer nanoparticles are reasonable and feasible, and in vitro experiments show an obvious sustained-release effect, which provides an experimental basis for future in vivo and in vitro studies.
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