脱氧氟尿苷脂质体的制备

目的建立脱氧氟尿苷(DFUR)脂质体的制备工艺。方法采用逆向蒸发法制备DFUR脂质体,并以包封率为参考指标,进行正交试验优化该脂质体的配方。以优化的配方制备脂质体,观察其微观形态,测定粒径、包封率及稳定性,并进行体外释药实验。结果制备DFUR脂质体的最佳配方为:卵磷脂/胆固醇(摩尔比)为2∶1,有机相/水相(体积比)为5∶1,DFUR浓度为2mg/ml,磷酸盐缓冲液pH值为7.0。以此配方制备,脂质体包封率可达52.15%。3批DFUR混悬液,粒径小于220nm的粒子比率均在70%以上,显微镜下观察可见,脂质体呈球形或椭圆形,粒径范围在0.15μm～1.00μm之间。4℃保存49d,脂质体的稳定性良好。其累积释放率远低于原料药浓度。结论已建立了DFUR脂质体的制备工艺,该工艺操作简便可靠,所需设备简单,稳定性较好,可用于包埋水溶性药物。

Preparation of Doxifluridine Liposome

Objective To develop a procedure for preparation of doxifluridine(DFUR)liposomes.Methods DFUR liposome was prepared by reverse phase evaporation technique, and the preparation procedure was optimized by orthogonal test using encapsulation efficiency as a reference index.The DFUR liposome prepared by the optimized procedure was observed for micromorphology, determined for particle size, encapsulation efficiency and stability, and subjected to release test in vitro.Results The optimal molar ratio of ovolecithin to cholesterol, volume ratio of organic phase to aqueous phase, DFUR concentration and pH value of PBS for preparation of DFUR liposome were 2 ∶ 1, 5 ∶ 1, 2 mg / ml and 7.0 respectively.The encapsulation efficiency of DFUR liposome prepared by the optimal formula reached 52.15%.All the percentages of particles at sizes of less than 220 nm in 3 batches of DFUR suspension were more than 70%.The prepared DFUR liposome was spherical or oval particles at sizes of 0.15～1.00 μm under microscope, and showed good stability after storage at 4℃ for 49 d.The cumulative release rate of prepared DFUR liposome was far lower than that of DFUR solution as a material.Conclusion A simple, reliable and stable procedure for preparation of DFUR liposome was developed, which needed only simple equipments and was suitable for embedding water-soluble drugs.