5-氟尿嘧啶-蛇葡萄素复方脂质体的制备

Preparation of 5-Fluorouracil and Ampelopsin Compound Liposome

关键词:  5-氟尿嘧啶  蛇葡萄素  复方脂质体  薄膜分散超声法  紫外分光光度法

Key words:  5-fluorouracil  ampelopsin  compound liposomes  film-dispersion-ultrasonic technique  ultraviolet spectroscopy

摘要:

目的 制备5-氟尿嘧啶-蛇葡萄素复方脂质体并建立同时测定2种药物含量的紫外分光光度法。方法 紫外分光光度法确定5-氟尿嘧啶和蛇葡萄素的测定条件。比较几种脂质体的制备方法，以包封率和粒径为指标，确定最优制备方法；采用正交设计进行优化处方和制备工艺。结果 采用紫外分光光度法测定5-氟尿嘧啶和蛇葡萄素，2种药物的加样回收率均在99%~102%之间。以薄膜分散超声法为制备方法，以单因素考察结合正交设计优选出的最佳处方和制备工艺，主药∶卵磷脂＝1∶20，卵磷脂∶胆固醇＝4∶1，磷脂浓度50 g·L^-1；维生素E的用量为5％，磷酸盐缓冲溶液pH为7.4。5-氟尿嘧啶和蛇葡萄素的包封率分别为(44.79±1.55)%和(75.47±0.91)%( n=3)；复方脂质体的粒径为(142±3.6)nm。5-氟尿嘧啶和蛇葡萄素的体外12 h 累积释放率分别为43.05%和60.24%。结论 将5-氟尿嘧啶和蛇葡萄素同时包封于脂质体制备成复方脂质体，所采用的制备工艺简单可行，重复性好，包封率较高。建立的紫外分光光度法可同时测定复方脂质体中的5-氟尿嘧啶和蛇葡萄素含量。

Abstract:

OBJECTIVE To study the preparation of 5-fluorouracil and ampelopsin compound liposome and to establish a ultraviolet spectroscopy for simultaneous determination of the two drugs. METHODS Based on the test of single factors, the optimized formulation of compound liposome was obtained by the orthogonal methodology. Entrapment ratio and diameter of the liposome were served as index. The entrapment efficiency of compound liposome was determined by means of Sephadex gel chromatography. The contents of 5-fluorouracil and ampelopsin were determined by ultraviolet spectroscopy. RESULTS Ultraviolet spectrophotometry was used for analyzing the amount of 5-fluorouracil and ampelopsin. The recovery of 5-fluorouracil and ampelopsin was in a range of 99%-102%. The compound liposomes were prepared by the film-dispersion- ultrasonic technique. The best craft produce was investigated by single factor and the optimal preparation conditions were as follows: drug∶lecithin=1∶20, lecithin∶cholesterol=4∶1, phospholipid concentration 50 g·L^-1, vitamin E 5%, pH 7.4 phosphate buffer 16 mL. The entrapment efficiencies of 5-fluorouracil and ampelopsin of compound liposome were (44.79±1.55)% and (75.47±0.91)% (n=3) , and the particle size was (142±3.6)nm. The in vitro 12 h accumulative release of 5- fluorouracil and ampelopsin were 43.05% and 60.24% of the total drug. CONCLUSION Film-dispersion-ultrasonic technique for the compound liposome preparation is simple and efficiency. Compound liposome has high entrapment efficiency and the quality of the liposome is controllable. This ultraviolet spectroscopy can be used for quality control of 5-fluorouracil and ampelopsin in the compound liposome.