物理化学学报 >> 2007, Vol. 23 >> Issue (05): 635-640.doi: 10.1016/S1872-1508(07)60040-0

研究论文 上一篇    下一篇

三种非甾体类抗炎药与脂质体的相互作用

杨昌英; 刘义; 李强国; 李林蔚   

  1. 三峡大学化学与生命科学学院, 湖北 宜昌 443002; 武汉大学化学与分子科学学院, 武汉 430072
  • 收稿日期:2006-09-21 修回日期:2006-12-28 发布日期:2007-04-28
  • 通讯作者: 刘义 E-mail:prof.liuyi@263.net

Interaction of Three Non-steroidal Anti-inflammatory Drugs with Egg Phosphatidylcholine Liposomes

YANG Chang-Ying; LIU Yi; LI Qiang-Guo; LI Lin-Wei   

  1. College of Chemistry and Life Science, Three Gorges University, Yichang 443002, Hubei Province, P. R. China; College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P. R. China
  • Received:2006-09-21 Revised:2006-12-28 Published:2007-04-28
  • Contact: LIU Yi E-mail:prof.liuyi@263.net

摘要: 以卵磷脂脂质体为生物膜模型, 分别采用二阶导数吸收光谱法和以1-苯胺基-8-萘磺酸铵(ANS)为探针的荧光光谱法, 研究了三种丙二酸类非甾体抗炎药吲哚美辛、舒林酸和托美丁与脂质体的相互作用. 药物的二阶导数吸收谱成沟槽型,在脂质体中沟槽变浅, 但波长基本上不移动, 表明药物结合在磷脂双层的表面而没有进入到脂双层内部. 在荧光光谱中, 抗炎药可以结合到脂质体上, 游离出ANS, 猝灭ANS 在脂质体中的强烈荧光, 表观猝灭常数KSVapp>10^12 L·mol^(-1); 药物先行结合到脂质体上后, 会降低ANS结合到脂质体上的机率. 同样表明药物可以结合到脂质体表面磷脂分子的头部, 结合能力的强弱与吸收谱得到的结果一致, 舒林酸最强, 吲哚美辛其次, 托美丁的结合能力较弱.

关键词: 脂质体, 非甾体抗炎药, 二阶导数吸收谱, 荧光光谱, ANS

Abstract: Second-derivative absorption spectra and steady-state fluorescence quenching were used to investigate the interaction between three anti-inflammatory drugs (NSAIDs), namely, indomethacin, sulindac and tolmetin, with egg phosphatidylcholine (EPC) liposomes, which served as a membrane mimetic system. The absorbance of drugs decreased with the addition of EPC liposomes and no shift was observed in the spectra, which indicated that drug molecules did not move to the less polar media constituted by hydrocarbon, but bound on the surface of phosphatidylcholine bilayer. Drugs had the ability to displace, in a dose-dependent manner, 1-anilino-8-naphthalene-sulfonate (ANS), a fluorescent anionic probe previously bound to the head group of phosphatidylcholine molecules. The existence of drugs in liposomes could inhibit the binding of ANS obviously. These factors suggested that the anti-inflammatory drugs could reach the surface of the bilayer, probably with the negative carboxyl group anchored near the phospholipid headgroup, and with the rest of the molecule buried partly in the membrane and aligned with the phospholipid aliphatic tails. These results provided evidence that NSAIDs reduced the ability of surface-active phospholipids to form a hydrophobic protective layer. The strongest interaction was observed between sulindac and liposomes.

Key words: Liposome, Non-steroidal anti-inflammatory drugs, Second-derivative absorption spectra, Fluorescence spectroscopy, ANS

MSC2000: 

  • O644