叶酸靶向含硼脂质体的制备及其包封率的测定

Studies on preparation of folate-targeted boron liposomes as potential delivery agents for neutron capture therapy

制备具有良好靶向性及包封率高的硼脂质体,为硼中子俘获治疗方法的研究与应用建立了一个有效的靶向给药途径。采用复乳法及薄膜—超声分散法制备叶酸靶向硼脂质体,利用高效液相色谱法检测4—羟基苯硼酸4—Hydroxyphenylboronicacid(HBA)脂质体、2—噻吩硼酸2—thiophenylboric acid(TBA)脂质体、4—叔丁基苯硼酸4—tert-Butylphenylboronic Acid(BBA)脂质体的含量及包封率,以包封率为评价指标,采用单因素法优化脂质体的制备处方和工艺条件。筛选出HBA、TBA、BBA最优的色谱条件,分别绘制出标准曲线,结果表明在1～100μg/mL范围内线性关系良好。HBA、TBA、BBA脂质体在最优制备处方和工艺条件下包封率分别为25.7%、38.9%、94.8%。BBA脂质体优化后的制备处方和工艺条件如下:胆固醇与磷脂质量比为1∶1,药脂比为1∶50,pH值为7.4,按该处方工艺制备的BBA脂质体包封率在94.8%。制备叶酸靶向脂质体的优选处方和制备工艺稳定可行,质量控制方法简单、准确,包封率高。

To prepare folate-targeted liposomes with high encapsulation efficiency is an effective targeted drug delivery agent for boron neutron capture therapy（BNCT）.The double emulsion method is used to prepare liposomes.The combination of thin film hydration and ultrasonic dispersion method is used to prepare liposomes loaded with HBA,TBA or BBA.The content and the encapsulation efficiency of HBA,TBA or BBA liposomes are evaluated by high performance liquid chromatography（HPLC）.As the basis of the encapsulation efficiency,the optimal conditions for preparing liposomes were explored by the single factor method.The optimal chromatographic conditions of the three drugs were filtered out.They had a good linear relation in a range of 1~100 μg/mL.The encapsulation efficiency of HBA,TBA and BBA liposomes were 25.7 %,38.9 % and 94.8 % at the optimal preparation and condition.The optimal conditions for preparing BBA liposomes are as follows： the mass ratio of cholesterol and phospholipid is 1∶1,the ratio of drug and lipid is 1∶50 and the optimal pH value is 7.4.The entrapment efficiency for BBA liposomes in the optimal groups reached 94.8 %.The technique of preparing folate-targeted liposomes is feasible and the method of quality control is simple and high accuracy.The liposomes appeare to be round,and well separated with high entrapment efficiency.