【摘要】 目的制备齐多夫定棕榈酸酯脂质体并考察其在小鼠体内的分布情况。方法采用乙醇注入法制备齐多夫定棕榈酸酯脂质体;采用HPLC法测定静脉注射后小鼠体内齐多夫定的质量浓度。结果脂质体包封率为95.2%,粒径为(75.6±42.2)nm。小鼠尾静脉分别注射齐多夫定棕榈酸酯脂质体30.0mg.kg-1和齐多夫定溶液15.85mg.kg-1后,体内消除半衰期脂质体组为16.4min,溶液组为5.74min;30min内脂质体组肝、脾、肾和脑(15min内)中齐多夫定的AUC值分别为溶液组的1.6倍、1.19倍、80%、1.8倍。结论采用乙醇注入法制备的齐多夫定棕榈酸酯脂质体包封率高,粒径均匀;可延长药物体内消除半衰期,提高了其在肝和脑的靶向性。齐多夫定棕榈酸酯脂质体有望成为一种理想的抗艾滋病制剂,值得进一步深入研究。更多还原

【Abstract】 Objective To prepare azidothymidine palmitate liposomes and observe its tissue distribution in mice.Methods The azidothymidine palmitate was incorporated into liposomes by ethanol injection method.The concentrations of azidothymidine in various organs were determined by reversed phase HPLC after i v administration.Results The entrapment efficiency of azidothymidine palmitate liposomes was 95.2%,the particle sizes of the liposomes was(75.6±42.2)nm.The azidothymidine palmitate liposomes and azidothymidine solution were injected intravenously at a dose of 30.0 mg·kg-1 and 15.85 mg·kg-1 to Kunming mice,respectively.The elimination half-life of liposomes and free azidothymidine solution was 16.4 and 5.74 min,respectively.Compared to azidothymidine solution,the AUC(0-30 min) in liver,spleen,kidney and brain(15 min) were 1.6,1.19,0.8 and 1.8 times,respectively.Conclusions Through the ethanol injection method,a high entrapment efficiency of azidothymidine palmitate liposomes is obtained.In vivo distribution studies indicated that the elimination half-life and the targetability of azidothymidine palmitate to liver and brain are significantly increased by the azidothymidine palmitate liposomes.Azidothymidine palmitate liposomes might be a promising candidate for anti-HIV therapy and worth further investigation.更多还原