Complexation of tauro- and glyco-conjugated bile salts with a-cyclodextrin and hydroxypropyl-a-cyclodextrin studied by affinity capillary electrophoresis and molecular modelling
Complexation of tauro- and glyco-conjugated bile salts with a-cyclodextrin and hydroxypropyl-a-cyclodextrin studied by affinity capillary electrophoresis and molecular modelling
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DOI：
10.1002/jssc.201100479
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发表时间：
2011-11-01
影响因子：
3.1
通讯作者：
Ostergaard, Jesper
中科院分区：
文献类型：
--
作者：
Holm, Rene;Schonbeck, Christian;Ostergaard, Jesper
用迁移率变化亲和毛细管电泳法研究了牛磺胆酸盐、牛磺酸脱氧胆酸盐、牛磺酸鹅去氧胆酸盐、甘胆酸盐、甘氨酸脱氧胆酸盐和甘鹅脱氧胆酸盐与α-环糊精和2-羟丙基-α-环糊精的相互作用。环糊精作为赋形剂用于增溶水溶性较差的药物物质。对于弱的分析配基相互作用，如共轭胆盐与环糊精的相互作用，准确测定稳定常数是一项挑战。介绍了一种校正背景电解液中高添加剂浓度引起的介质效应的新方法。使用前列腺素A1作为相互作用的标记分子提供了一种比常用的基于粘度或流动比的方法更令人满意的校正方法。选择相互作用的标记而不是非相互作用的标记，以避免非相互作用属性的困难验证。所研究的胆盐均与α-环糊精和2-羟丙基-α-环糊精相互作用。得到的稳定常数范围为14~95m-1，与取代环糊精的亲和力略高。分子模拟表明，这两个物种之间的相互作用涉及胆盐的侧链。综上所述，这些结果表明，少量胆盐介导的物质在小肠内从a-环糊精复合体中置换出来。
The interaction of the bile salts taurocholate, taurodeoxycholate, taurochenodeoxycholate, glycocholate, glycodeoxycholate, and glycochenodeoxycholate present in man, dog, and rat with a-cyclodextrin and 2-hydroxypropyl-a-cyclodextrin was investigated by mobility shift affinity capillary electrophoresis. The cyclodextrins are applied as excipients for solubilisation of drug substances with poor aqueous solubility. Accurate determination of stability constants is challenging for weak analyteligand interactions such as the conjugated bile salt a-cyclodextrin interactions. A new approach for correction of medium effects due to the high additive concentrations in the background electrolyte was introduced. The use of prostaglandin A1 as an interacting marker molecule offered a more satisfactory approach for correction than the commonly employed methods based on viscosity or current ratios. The interacting marker was chosen over a non-interacting marker to avoid the difficult validation of the non-interacting properties. The investigated bile salts all interacted with a-cyclodextrin and 2-hydroxypropyl-a-cyclodextrin. Stability constants ranging from 14 to 95?M-1 were obtained with slightly higher affinities toward the substituted cyclodextrin. Molecular modelling demonstrated that the interaction between the two species involves the side chain of the bile salt. All together, these results indicate minor bile salt-mediated displacement of substances from a-cyclodextrin complexes in the small intestine.