肺靶向阿奇霉素脂质体的制备及其在小鼠体内的分布

Preparation of lung targeting azithromycin liposomes and its tissue distribution in mice

目的 研究肺靶向阿奇霉素阳离子脂质体的制备方法并考察其在小鼠体内的分布。方法 利用旋转薄 膜 冻融法制备肺靶向阿奇霉素脂质体。用高效液相色谱法测定给药后小鼠体内各组织中的药物浓度。结果 制得的脂质体平均粒径为6.582μm,表面电荷为+19.5mV,包封率大于75%,稳定性好。药物体外释药符合Higuchi方 程。小鼠尾静脉给药后,阳离子脂质体主要被肺摄取,在肺部的滞留时间明显延长,AUC值约为阿奇霉素溶液的8.4 倍。结论采用薄膜 冻融法,添加十八胺可制得具有较高包封率及稳定性的阿奇霉素阳离子脂质体,在小鼠肺部的分布优于注射液,能达到肺靶向目的。

Aim To prepare lung targeting azithromy cin cationic liposomes and to observe its tissue distribution in mice. Methods The azithromycin cationic liposomes were prepared by th in film method with freeze-thawing steps. HPLC method was established and valid ated for the determination of azithromycin in tissues of mice. Results The particle size of the liposomes was 6.582 μm with ζ potential of +19.5 mV. The entrapment efficiency was more than 75%. The liposomes was stable in 6 months stored at 4 ℃. The release in vitro was characterized by Higuchi equation. Azithromycin liposomes and free azithr omycin solution were injected intravenously at a dose of 80 mg·kg -1 t o mice. Compared with solution, liposomes were characterized by slower clearance , increased half-life and the AUC increased by 7.4 fold in lung. Conclusion Thin film method with freeze-thawing steps could in crease the entrapment efficiency and increase the particle size of azithromycin liposomes. After modification of lipid membrane with stearylamine, the cationic liposomes were prepared. The azithromycin concentration and AUC increased in lun g after iv administration to mice of the cationic liposomes. This offered a good information for preparing liposomes targeting on the lung.