硬脂醇半乳糖苷修饰吉西他滨纳米脂质体的制备及处方优化

Preparation and Formula Optimization of Stearyl Alcohol Galactoside Modified Gemcitabine Hydrochloride Nano Liposome

关键词:  硬脂醇半乳糖苷  盐酸吉西他滨  纳米脂质体  硫酸铵梯度法  Box-Behnken响应面法

Key words:  stearyl alcohol galactose  emcitabine hydrochlorid  nano liposome  ammonium sulfate gradient method  Box-Behnken

摘要:

目的 制备硬脂醇半乳糖苷修饰的盐酸吉西他滨纳米脂质体(18-GGNL)，并采用响应面法优化其处方工艺。方法 用硫酸铵梯度法制备18-GGNL，以包封率为评价指标，运用Box-Behnken响应面设计法对处方进行优化，并对其包封率、形态、粒径、稳定性和体外释放度进行综合评价。结果 得到最优处方为磷脂与胆固醇的质量比为3.10︰1，硫酸铵浓度0.19 mol?L^-1，脂物比为20.99︰1，所得的优化脂质体平均包封率为(70.8±0.95)%，平均粒径为(89.5±5.3)nm，粒径分布较窄，稳定性好且具有缓释特性。结论 以硫酸铵梯度法制备的18-GGNL理化性质良好。

Abstract:

To prepare stearyl alcohol galactosidase modified gemcitabine hydrochloride nanoliposomes (18-GGNL) and optimize the prescription process using response surface methodology. METHODS The 18-GGNL was prepared by (NH4)2SO4 gradient method, the entrapment efficiency as the evaluation index, Box-Behnken response surface design method was used to optimize the formulation. The 18-GGNL was evaluated by encapsulation efficiency, drug loading, morphology, particle size, stability, and in vitro release. RESULTS The optimized formulation was as follows: the concentration of phospholipid was 3.10︰1, concentration of ammonium sulfate was 0.19 mol?L^-1, lipid ratio was 20.99︰1. The average of liposome entrapment efficiency was (70.8±0.95)%, the average particle size was(89.5±5.3)nm, the particle size distribution was narrow, good stability and slow release characteristics. CONCLUSION The (NH4)2SO4 gradient prepares 18-GGNL with good physical and chemical properties。