斑蝥素半乳糖化脂质体制备工艺研究

Preparation process of galactosylated liposome of modified cantharidin

目的优选斑蝥素半乳糖化脂质体(Lac-CTD-lips)的最佳处方配比和制备工艺,并建立其含量测定的方法。方法采用薄膜分散法制备Lac-CTD-lips,采用GC-MS法建立斑蝥素含量测定的方法,以斑蝥素的包封率为评价指标,通过单因素考察结合正交试验,优化Lac-CTD-lips的制备工艺,并对其进行表征、包封率、粒径、Zeta电位考察。结果 Lac-CTD-lips最佳处方为斑蝥素-氢化大豆磷脂-胆固醇(1∶20∶5)、10%半乳糖苷;最佳工艺为50℃成膜,30 m L pH 6.0的PBS溶液洗膜,40℃下水合1.5 h。所得Lac-CTD-lips外观呈淡蓝色乳光,粒子形态呈球型,表面较圆整,无粘连。平均粒径为(123.9±4.8)nm(n=3),粒径分布呈单峰,Zeta电位为(-0.36±0.81)m V(n=3),包封率可达75%以上。结论 GC-MS适用于斑蝥素的定量测定,正交试验优选的制备工艺稳定可靠,所得的Lac-CTD-lips包封率较高、粒径小,外观形态好。

Objective To optimize the formulation ratio and preparation process of galactosylated cantharidin liposome（Lac-CTDlips） and establish its methodology for content determination. Methods The method of determination of GC-MS cantharidin content was established by film dispersion method. The entrapment efficiency of cantharidin was evaluated as an index. The preparation process of Lac-CTD-lips was optimized by single factor and orthogonal experiments. Its surface characteristics, encapsulation efficiency, particle size, and Zeta potential were also investigated. Results The best prescription was as follow： cantharidin： hydrogenated soya lecithin：cholesterol at 1∶20∶5, 10% galactoside, film-forming at 50 ℃, film cleaning with 30 m L of PBS solution of pH 6.0, and hydartion at 40 ℃ for 1.5 h. The resulting liposomes exhibited a pale blue opalescent appearance, a spherical particle morphology, and a more rounded surface with no adhesion. The average particle size was（123.9 ± 4.8） nm（n = 3）, the particle size distribution was single-peak, the zeta potential was（-0.36 ± 0.81） m V（n = 3）, and the encapsulation efficiency was over 75%. Conclusion GC-MS is suitable for the determination and analysis of cantharidin content. The optimal preparation technology from orthogonal experiment is stable and reliable. The obtained liposomes have higher encapsulation efficiency, small particle size, and good appearance.