鼻用氟尿嘧啶壳聚糖微球的制备及其特性研究

目的: 以壳聚糖为载体材料,氟尿嘧啶为模型药物, 制备鼻腔给药脑靶向微球.方法: 以液体石蜡为油相,span-80为乳化剂,采用乳化化学交联技术制备氟尿嘧啶鼻用微球.正交实验设计优化制备工艺,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.测定纤毛输送速率来评价微球的黏膜粘附力.结果:所得微球形态良好,粒径分布较为均匀,平均粒径(43±4) μm,载药量38.5%±1.0%,包封率79.0%±1.8%.体外释放符合Higuichi方程Q=0.103 5t1/2 0.028 4 (r=0.996 5).壳聚糖微球具有良好的生物粘附性,可显著降低纤毛输送速率(P<0.01),有效地延长微球在鼻腔的滞留时间.结论:所优化的制备工艺稳定,包封率较高,适于鼻黏膜用氟尿嘧啶壳聚糖微球的制备.壳聚糖是良好的鼻用制剂的载体材料,应用前景广阔.

Preparation and properties of 5-fluorouracil-loaded chitosan microspheres for the intranasal administration

OBJECTIVE: To study the preparation technique and release characteristic of 5-fluorouracil loaded chitosan microspheres for the intranasal administration. METHODS:Using the liquid paraffin as the oil phase,and span-80 as the emuifier; 5-fluorouracil-loaded chitosan microspheres were achieved by emulsion-chemical crosslink technique. The orthogonal experimental design was applied to optimize the preparation procedure. Dynamic dialysis method was used to determine the releasing characteristic of microspheres in vitro and it influencing factors.Swelling behavior was expressed by swelling ratio.The degree of mucoadhesion was investigated by determining the mucociliary transport rate(MTR) of the microparticle across a frog palate. RESULTS: Microspheres with a good shape and narrow size distribution were prepared. The average diameter was (43+/-4) microm. The drug loading was 38.5%+/-1.0%. The entrapment efficiency was 79.0%+/-1.8%.The drug release profile in vitro could be described by Higuichi equation Q=0.1035t(1/2)+0.0284 (r=0.9965). Chitosan had good mucoadhesive property and caused a significant reduction in MTR(P<0.01). CONCLUSION: The optimized preparation technique is stable and has a high entrapment efficiency. So it could be used to prepare 5-fluorouracil-loaded chitosan microspheres for the intranasal administration. Chitosan is a good material for nasal preparation and has prospective development in the pharmaceutical field.