[Preparation of lung targeting azithromycin liposomes and its tissue distribution in mice].
[Preparation of lung targeting azithromycin liposomes and its tissue distribution in mice].
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发表时间：
2005-03
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通讯作者：
Jiansong Wang;Jia-bi Zhu;Ruicong Lu;W. Shen
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作者：
Jiansong Wang;Jia-bi Zhu;Ruicong Lu;W. Shen
目的制备肺靶向阿奇霉素阳离子脂质体，并观察其在小鼠体内的组织分布。方法采用冻融法制备阿奇霉素阳离子脂质体。建立并验证了高效液相色谱法测定小鼠组织中阿奇霉素的含量。结果脂质体粒径为6.582微米，zeta电位为+19.5 mV。捕集效率达75%以上。脂质体在4℃条件下贮存6个月稳定，体外释放用Higuchi方程表征。小鼠静脉注射阿奇霉素脂质体和游离阿奇霉素溶液，剂量为80mg x kg（-1）。与溶液相比，脂质体清除率较慢，半衰期延长，肺内AUC增加7.4倍。结论冻融步骤的薄膜法可提高阿奇霉素脂质体的包封效率，增大其粒径。用硬脂胺修饰脂膜后，制备了阳离子脂质体。阳离子脂质体给药后，小鼠肺内阿奇霉素浓度和AUC升高。这为制备靶向肺的脂质体提供了良好的信息。
AIM To prepare lung targeting azithromycin cationic liposomes and to observe its tissue distribution in mice. METHODS The azithromycin cationic liposomes were prepared by thin film method with freeze-thawing steps. HPLC method was established and validated for the determination of azithromycin in tissues of mice. RESULTS The particle size of the liposomes was 6.582 microm with zeta potential of +19.5 mV. The entrapment efficiency was more than 75%. The liposomes was stable in 6 months stored at 4 degrees C. The release in vitro was characterized by Higuchi equation. Azithromycin liposomes and free azithromycin solution were injected intravenously at a dose of 80 mg x kg(-1) to 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 increase 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 lung after iv administration to mice of the cationic liposomes. This offered a good information for preparing liposomes targeting on the lung.