盐酸吉西他滨隐形脂质体的制备及工艺优化  

Preparation and process optimization of gemcitabine hydrochloride stealth liposomes

作　　者：郑钦[1] 陶静[1] 张亦斌[1] 邓盛齐[1] 

机构地区：[1]抗生素研究与再评价四川省重点实验室,四川抗菌素工业研究所,成都大学,成都610052

出　　处：《中国抗生素杂志》2017年第5期382-388,共7页Chinese Journal of Antibiotics

摘　　要：目的应用响应面分析法优化盐酸吉西他滨隐形脂质体的制备条件。方法结合改良薄膜法和冻融法制备盐酸吉西他滨隐形脂质体,利用Plackett-Burman实验设计法确定显著影响药物包封率的因素,即脂药比(W/W),HSPC/DSPE-PEG2k(W/W),脂质比(W/W),并对其进行3因素5水平的中心组合实验,筛选最佳处方工艺,并绘制体外释药曲线。结果最优处方工艺条件为磷脂:药物:胆固醇:DSPE-PEG2k为60:3:20:4.8(W/W),PBS浓度0.1mmol/L,水化时间1h,探头超声时间3min(80W,3s/3s),冻融4次;在此优化条件下,包封率为65.85%±0.48%,较优化前提高近25%。体外释放动力学符合双指数方程,具有一定缓释作用。结论响应面分析法可有效平衡各因素之间的相互影响,适用于脂质体制备工艺及处方筛选。Objective Two statistical designs were used in this case study. The anti-cancer drug gemcitabine hydrochloride was used as a model compound to optimize the formulation of liposomes, and to investigate the characteristics of drug release in vitro. Methods The modified thin film method and the freeze thaw method was used to prepare gemcitabine hydrochloride stealth liposomes. First design （Plackett-Burman） was used to determine the factors that significantly affected the drug entrapment efficiency. It was discovered that the mass ratio of hydrogenated soybean phospholipids （HSPE）, cholesterol, drugs and DSPE-PEG2k had significant effects on the drug encapsulation efficiency. This allowed the use of a central composite design （CCD） to elucidate the relationship between the these factors and the encapsulation efficiency. The drug release curve of the preparated gemcitabine hydrochloride stealth liposomes was drawn. Results Using this developed model, the optimal conditions included that the mass ratio of HSPE： cholesterol：drugs： DSPE-PEG2k was 60：3：20：4.8; the PBS concentration was 0.1mmol/L; the hydration time was lh; the ultrasonic time was 3min （80W, 3s/3s）; and the freeze-thaw cycles were 4 times. Under the optimized conditions, encapsulation efficiency was 65.85%±0.48%, which increased by nearly 25% compared with the original condition, and the release curve was fitted with ambiexponent equation. Conclusion Response surface analysis can effectively balance the interactions between various factors, and thus is suitable for the liposome preparation process and prescription screening.

关 键 词：盐酸吉西他滨 隐形脂质体 响应面法 包封率 

分 类 号：R979.1[医药卫生—药品]