改良法制备5-氟尿嘧啶磁性纳米脂质体

Improved preparation method of magnetic nano-liposome loaded with 5-fluorouracil

目的探讨5-氟尿嘧啶磁性纳米脂质体（MNLF）的最佳制备方法，并观察其理化性能。方法采用正交设计对筛选出的制备工艺进行优化，以磁性脂质体的包封率和粒径分布为指标综合评价，以药物与磷脂的比例、表面活性剂的浓度及油水相的比例、冻融温度等为考察指标，分析了不同制备方法对脂质体性质的影响。最后选用逆向蒸发法结合冻融法制备MNLF，最佳方案为A3B3C2D2及蛋黄卵磷脂（PC）：去氧胆酸钠（SD）为10：1，冷冻温度为-10℃，以包封率、外观、粒径变化、渗漏率、胶体ζ电位和pH值等为评价指标，对MNLF的物理化学稳定性进行研究。结果制备的MNLF的平均粒径为450ntn，平均包封率为69．5％，ζ电位为-39．0mV，pH值为6．91，有较好的稳定性，磁响应性好。结论以改良的逆相蒸发法＋冻融法制备的MNLF粒径小、包封率高、磁响应性好。

Objective To explore the optimal preparation technology and to investigate the physical and chemical characteristics of magnetic nano-liposome loaded with 5-fluorouracil （MNLF）. Methods MNLF was prepared by reverse phase evaporation method combined With frozen-thawed method and the preparation procedure was optimized by orthogonal design with the encapsulation efficiency and size distribution as synthetic indexes ,also with different ratio of water to lipid,ratio of drug to lipid and different densities of surface active agent and frozen-thawed temperature as consideration factors. At last MNLF was prepared by the method of modified reverse phase evaporation method combined with frozen-thawed method. The optimized method was A3 B3 C2 D2, PC：SD ratio 10：1 and frozen-thawed temperature -10℃. The appearance, particle size, leakage ratio, colloid zeta potential and pH value were studied to evaluate the physic-chemical stability of MNLF. Results The average diameter of MNLF and its encapsulation ratio were 450 nm and 69.5% respectively. The zeta potential and pH were -39.0 mv and 6.91 respectively. It was showed that MNLF was stable and had good magnetic responsibility. Conclusion The MNLF prepared by reverse phase evaporation method combined with frozen-thawed method has small size, high encaps.ulation efficiency and good magnetic responsibility.