[Preparation of lung targeting azithromycin liposomes and its tissue distribution in mice].
OBJECTIVE
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.


CONCLUSIONS
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.
Wang
Jian-song
JS
Institute of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China. wjiansong@hotmail.com
Zhu
Jia-bi
JB
Lu
Rui-qin
RQ
Shen
Wei
W
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D017963:Azithromycin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D002412:Cations; D004337:Drug Carriers; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D005260:Female; D008081:Liposomes; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D010316:Particle Size; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; D002412:Cations; D004337:Drug Carriers; D008081:Liposomes; D017963:Azithromycin