冰片修饰的葛根素脂质体的制备及脑组织分布研究

Preparation and Brain Distribution of Borneol Modified Puerarin Liposomes

关键词:  冰片  葛根素  脂质体  正交设计  脑组织分布

Key words:  borneol  puerarin  liposomes  orthogonal design  brain distribution

摘要:

目的 制备冰片(borneol，BO)修饰的葛根素(puerarin，Pue)脂质体(BO-Pue-Lips)，进行理化性质考察及大鼠体内脑组织分布研究。方法 采用薄膜分散法制备BO-Pue-Lips，通过正交设计，以包封率和载药量为评价指标优化处方工艺。以Pue混悬液和(BO-Pue)混悬液为对照组，测定大鼠尾静脉给药BO-Pue-Lips的脑组织浓度。结果 制备BO-Pue-Lips的优化条件为Pue与卵磷脂质量比为1∶10，胆固醇与卵磷脂质量比为1∶4，制备温度为40 ℃。按优化条件所制备的BO-Pue-Lips粒径为(112.97±0.89)nm，Zeta电位为(-7.48±0.49)mV，包封率为(73.47±1.75)%，载药量为(5.55±0.13)%，药物释放曲线符合Weibull方程模型。脑组织分布结果显示，Pue、BO-Pue和BO-Pue-Lips的T_1/2分别为(0.61±0.22)h，(0.55±0.27)h和(1.80±0.17)h，AUC_0→t分别为(68.59±1.09)μg·h·g^-1，(72.70±2.63)μg·h·g^-1和(137.68±10.17)μg·h·g^-1，CL分别为(0.29±0.01)L·h^-1·kg^-1，(0.27±0.02)L·h^-1·kg^-1和(0.13±0.01)L·h^-1·kg^-1，MRT分别为(0.93±0.05)h，(0.97±0.02)h和(1.80±0.05)h。结论 采用薄膜分散法成功制备了BO-Pue-Lips，确定了最优制备处方和制备工艺。BO-Pue-Lips给药后显著提高葛根素脑组织蓄积量，延长药物在脑中的滞留时间，具有良好的脑靶向性。

Abstract:

OBJECTIVE To prepare borneol modified puerarin liposomes(BO-Pue-Lips) with optimization, and evaluate the concentration in brain of the drug liposomes in rats. METHODS The BO-Pue-Lips were prepared with the thin-film rehydration method and were optimized through orthogonal test according to entrapment efficiency and drug loading of BO-Pue-Lips. Using puerarin(Pue) suspension and borneol puerarin(BO-Pue) suspension as control, the concentration in brain of BO-Pue-Lips after intravenous administration in rats were studied. RESULTS The optimal conditions for preparation of BO-Pue-Lips were Pue-soybean phospholipids(1︰10), cholesterol-soybean phospholipids(1︰4), and the hydration temperature was 40 ℃. The mean particle size of the resulted BO-Pue-Lips was (112.97±0.89)nm and Zeta potential was (-7.48±0.49)mV, the average entrapment efficiency and drug-loading was (73.47±1.75)% and (5.55±0.13)%, respectively. The profiles of release in vitro was expressed well by Weibull equation. Results of distribution in brain showed that T_1/2of Pue, BO-Pue and BO-Pue-Lips were (0.61±0.22)h, (0.55±0.27)h and (1.80±0.17)h, AUC_0→twere (68.59±1.09)μg·h·g^-1, (72.70±2.63)μg·h·g^-1and (137.68±10.17)μg·h·g^-1, CL were (0.29±0.01)L·h^-1·kg^-1, (0.27±0.02)L·h^-1·kg^-1and (0.13±0.01)L·h^-1·kg^-1, MRT were (0.93±0.05)h, (0.97±0.02)h and (1.80±0.05)h. CONCLUSION An optimized liposomes drug delivery system is obtained by thin-film rehydration method. The preparation and preparation process are selected and optimized. The liposomes after intravenous administration might increase the concentration, prolong circulation time and have a good targeting efficiency in brain.