【摘要】 目的 :以壳聚糖为载体材料 ,5 氟脲嘧啶为模型药物 ,制备鼻腔给药脑靶向微球并考察其体外释放。方法 :采用乳化化学交联法制备氟脲嘧啶鼻用微球 ,正交实验设计中引入理想函数优化制备工艺 ,扫描电镜观察微球表面形态 ,动态透析法检测微球的体外释放特性及其影响因素。用微球吸水能力表示微球的溶胀度。结果 :所得微球形态良好 ,粒径分布窄 ,平均粒径为 4 3 2 0± 4 17μm ,载药量为 (38 4 8± 1 0 3) % ,包封率为 (78 96± 1 77) %。体外释放符合Higuichi方程Q =0 10 35t1/2 +0 0 2 84 ,r=0 996 5。体外释放初始阶段释药快 ,遵守溶胀控制机理 ,释放后期释药减慢 ,遵守扩散控制机理。结论 :所优化的制备工艺稳定 ,包封率较高 ,适于鼻粘膜用氟脲嘧啶壳聚糖微球的制备。更多还原

【Abstract】 AIM:To study chitosan used as a carrier,5- fluorouracil as a model drug,the preparation technique and release characteristic of 5- fluorouracil-loaded chitosan microspheres for the intranasal administration.METHOD: 5-Fluorouracil-loaded chitosan microspheres were achieved by emulsion-chemical crosslink technique.The orthogonal experimental design was applied to optimize the preparation procedure.The desirability function was introduced as a total index for the multiple variable of microsphere formulation.The surface morphology of the microspheres was observed by scanning electron microscope.Dynamic dialysis method was used to determine the releasing characteristic of microspheres in vitro and it influencing fators.Swelling behavior was expressed by swelling ratio.RESULT: Microspheres with a good shape and narrow size distribution were prepared.The average diameter was 43.2±4.17 μm.The drug loading was (38.48±1.03)%.The entrappment efficiency was (78.96±1.77)%.The drug release profile in vitro could be described by Higuichi eqution Q=0.1035t 1/2+0.0284(r=0.9965).Drug release was fast at the initial period in parallel to swelling behavior,however,the release was slow at the later time period followed by a diffusion-controlled mechanism. CONCLUSION: The optimized technique has a good reproducibility and a high entrappment efficiency,so it could be used to prepare 5-fluorouracil-loaded chitosan microspheres for the intranasal administration. [更多还原