[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.