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为了考察药物5-氟尿嘧啶(5-Fu)与吲哚美辛(IDMC)的协同作用,采用超临界流体强制分散溶液技术(SEDS),以二氯甲烷/二甲亚砜为共溶剂,制备了复合5-Fu和IDMC的L-聚乳酸(PLLA)微球。利用单因素法探索了制备复合微球的最佳外部条件,通过表面形貌、载药量、粒径分布、释放性能的检测和体外细胞实验来表征微球的各项性能。结果表明:当共溶剂二氯甲烷/二甲亚砜比例为30∶1时,制备该微球的优化条件为39℃、14 MPa;微球形貌呈类球形,粒径分布在0.5~5μm;复合IDMC后微球具有更优良的缓释效果;载药微球对A549细胞系增殖有明显的抑制作用,但与复合IDMC前后微球共培养的2组细胞的相对生长速率(RGR)无显著性差异。
In order to investigate the synergistic effect of the drug 5-fluorouracil (5-Fu) and indomethacin (IDMC), supercritical fluid forced dispersion technique (SEDS) and methylene chloride / dimethylsulfoxide L-polylactic acid (PLLA) microspheres complexed with 5-Fu and IDMC. The optimum external conditions for preparation of composite microspheres were explored by single factor method. The microspheres’ properties were characterized by surface morphology, drug loading, particle size distribution, release properties and in vitro cell experiments. The results showed that when the proportion of dichloromethane / dimethylsulfoxide was 30:1, the optimal conditions for the preparation of this microsphere were 39 ℃ and 14 MPa. The morphology of the microsphere was spherical and the particle size distribution was 0.5 ~ 5μm ; The microspheres with composite IDMC had better sustained-release effect; the drug-loaded microspheres significantly inhibited the proliferation of A549 cell line, but the relative growth rate (RGR) of the two groups co-cultured with IDMC Significant difference.