肺靶向羟基喜树碱脂质体的制备及体外释药性质研究

Study on Preparation and in Vitro Release Behavior of Lung Targeting Hydroxycamptothecin Liposomes

目的研究肺靶向羟基喜树碱阳离子脂质体的制备方法并考察其体外释药性质。方法采用薄膜-冻融法制备羟基喜树碱脂质体;用D-甘露糖修饰脂质体并添加适量十八胺调节脂质体表面电荷;用葡聚糖凝胶柱-高效液相色谱法测定包封率;用正交实验优选处方;用透析法考察药物体外释放性质。结果制得的脂质体平均粒径为2.286μm,表面电荷为+21.5 mV,包封率大于65%,稳定性好。药物体外释药符合Higuchi方程。结论采用薄膜-冻融法,用D-甘露糖修饰并添加十八胺可制得具有较高包封率及稳定性的羟基喜树碱脂质体,有助于提高羟基喜树碱的肺靶向性。

OBJECTIVE To prepare lung targeting hydroxycamptothecin （HCPT） cationic liposomes and study the release of HCPT in vitro. METHODS The hydroxycamptothecin liposomes were prepared by thin film method with freeze-thawing steps. D- mannose was used to coat the liposomes for lung targeting action and lipid membrane was modified with stearylamine. Unloaded hydroxyeamptothecin were separated by sephadex G50 chromatography. HPLC method was used to determine the entrapment efficiency of hydroxycamptothecin liposomes. Orthogonal design was used to select the optimum formulation. Dialysis was used to study the release of HCPT in vitro. RESULTS The prepared hydroxycamptotheein liposomes demonstrated good stability and encapsulation efficiency was more than 65%. The average size was 2. 286 μm and the Zeta potential of the modified hydroxycamptothecin liposomes was ＋ 21.5 inV. The release in vitro was characterized by Higuehi equation. CONCLUSION Thin film method with freeze-thawing steps could increase the entrapment efficiency and stability of hydroxycamptotheein liposomes after modification of lipid membrane with D-mannose and stearylamine. It was valuable to be further studied for lung target.