去氢骆驼蓬碱脂质体的制备和体外释放特性

Preparation of Harmine Liposomes and Its Release Characteristics in Vitro

目的:研究去氢骆驼蓬碱(harmine,HM)脂质体的制备工艺和体外释放特性。方法:运用薄膜分散-pH值梯度法制备HM-脂质体以及高速离心法分离脂质体与游离药物,并测定其包封率;借助综合评分法,评价其粒径、多分散系数、包封率、载药量指标;运用正交优化实验法考察磷脂-胆固醇与药-脂比、超声时间、外相pH值对脂质体的影响,遴选最优工艺处方,评价脂质体与原料药的体外释放情况。结果:最优处方因素为磷脂-胆固醇比值为4∶1,超声时间为300s,药-脂比值为1∶5,外相pH值为6.8,即X13X23X32X43,经实验验证其粒径为(155.0±14.5)nm,多分散系数为0.148±0.011),包封率为(80.90±0.01)%,载药量为(11.16±0.01)%;其原料药0.5h累积释放百分比大于50%,不到2h已全部释放,而优化后的脂质体在1h内其累积释放百分比大于50%,4h后释放完成。结论:采用薄膜分散-pH值梯度法,以最优处方制得HM-脂质体,其粒径大小适中、形态均匀,包封率和载药量相对较高,体外释放显示具有较好的缓释特性。

Objective：To investigate the optimization of preparation process of harmine liposomes and to compare the in vitro release of HM with liposomes. Methods： HM liposomes were prepared by film dispersion-pH gradient method. The liposomes and free drug were separated by high-speed centrifuge. Then the encapsulation efficiency was measured. By integrated score method. The orthogonal design method was carried out to evaluate the influence of the phospholipids on cholesterol weight ratio, the drug to lipid weight ratio, ultrasonic time and pH value of external water. Particle size, polydispersity, encapsulation efficiency and drug loading were selected for indexes. Results： The best formulation is as follows“phospholipids to cholesterol mass ratio of 4：1 ”, “probe ultrasound time of 300 s”, “drug to lipid mass ratio of 1：5”,“pH value of external water of 6.8”. Particle size of （155.0± 14.5）nm, polydispersity of （0.148± 0.011）, encapsulation efficiency of （80.90±0.01）% and drug loading of （11.16±0.01）%. Half an hour later the release of free drug was more than 50%, and in less than 2 h free drug released all. Liposomes were released about 50% in lh, and about 4h later the HM liposomes released completely. Conclusion： By film dispersion-pH gradient method, the HM liposomes of optimal formulation had medium particle size, a higher encapsulation efficiency and drug loading. Besides, the in vitro release demonstrated its sustained-release efficacy.