石莉,魏守刚,李乐,王绍宁,关敏怡,邓意辉
SHI Li1,WEI Shou-gang2,LI Le1,WANG Shao-ning2,GUAN Min-yi2,DENG Yi-hui2(1.Liaoning Institute of Pharmaceutical Industry

• 1:辽宁省药物研究院
• 2:沈阳药科大学药学院

摘要(Abstract)：

目的制备齐多夫定棕榈酸酯(zidovudine palmitate,AZTP)纳米乳剂并考察其在小鼠体内药动学与组织分布情况。方法微射流法制备AZTP纳米乳剂,采用高效液相色谱法测定静脉注射后小鼠体内齐多夫定(zidovudine,AZT)的质量浓度;采用DAS2.1.1药动学程序计算药动学参数,并以相对摄取率(re)为指标,评价AZTP纳米乳剂的靶向性。结果本法制备的AZTP纳米乳剂为乳白色半透明混悬液,无油滴,未分层,平均粒径为(55.3±26.0)nm,包封率为98.4%。小鼠尾静脉分别注射AZTP纳米乳剂和AZT溶液后,体内消除半衰期分别为13.44和23.47 min。与AZT溶液相比,纳米乳剂组在血浆、心、肝、脾、肺、肾和脑的re值分别为1.46、1.52、2.75、2.20、1.59、0.76、2.57。结论采用微射流法制备的AZTP纳米乳剂外观良好,粒径均匀;可延长药物体内消除半衰期,提高其在肝、脑和脾中的靶向性。AZTP纳米乳剂有望成为一种理想的抗艾滋病制剂,值得进一步深入研究。
Objective To prepare zidovudine palmitate(AZTP)nanoemlsions and observe its pharmacokinetics and tissue distributions in mice. Methods The AZTP nanoemlsions were prepared by microfluid method.The concentrations of AZT in plasma and tissues were determined by reversed phase HPLC after i.v.administration.The parameters of pharmacokinetics were calculated by DAS2.1.1.And the concentration-averaged overall drug relative tissue exposure(re)was used to evaluate the targetability of AZT in the AZTP nanoemlsions. Results The AZTP nanoemlsions which were prepared by microfluid method were milky and semitransparent liquid without oil drop and substratification.The mean diameter of nanoemlsions was(55.3±26.0)nm.The encapsulation efficiency was 98.4%.The AZTP nanoemlsions and zidovudine(AZT)solution were injected intravenously into KM mice,respectively.The elimination half-life of nanoemlsions and AZT solution were 13.44 min and 23.47 min,separately.Compared to AZT control solution,the re value of AZTP nanoemlsions in plasma,heart,liver,spleen,lung,kidney and brain were 1.46,1.52,2.75,2.20,1.59,0.76,2.57,respectively. Conclusions Through microfluid method,a fine appearance and well-distributed particles of AZTP nanoemlsions are obtained.In vivo distribution studies indicate that the elimination half-life and the targetability of AZTP to liver,brain and spleen are significantly increased by the AZTP nanoemlsions.AZTP nanoemlsions may be a promising candidate for anti-HIV therapy and worthy of further investigation.

关键词(KeyWords)： 齐多夫定棕榈酸酯;纳米乳剂;微射流法;体内分布;艾滋病
zidovudine palmitate;nanoemlsion;microfluid;in vivo distribution;AIDS

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目(30371694)

作者(Author): 石莉,魏守刚,李乐,王绍宁,关敏怡,邓意辉
SHI Li1,WEI Shou-gang2,LI Le1,WANG Shao-ning2,GUAN Min-yi2,DENG Yi-hui2(1.Liaoning Institute of Pharmaceutical Industry

DOI: 10.14066/j.cnki.cn21-1349/r.2012.09.012

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