Liu X Y, Yang Q, Kamo N, Miyake J
National Institute for Advanced Interdisciplinary Research, Agency of Industrial Science and Technology, Tsukuba, Ibaraki, Japan.
J Chromatogr A. 2001 Apr 13;913(1-2):123-31. doi: 10.1016/s0021-9673(00)01266-8.
Immobilized liposome chromatography (ILC) has been proven to be a useful method for the study or rapid screening of drug-membrane interactions. To obtain an adequate liposomal membrane phase for ILC, unilamellar liposomes were immobilized in gel beads by avidin-biotin binding. The retardation of 15 basic drugs on the liposome column could be converted to membrane partitioning coefficients, K(LM). The effects of small or large unilamellar liposomes and multilamellar liposomes on the drug-membrane partitioning were compared. The K(LM) values for both small and large liposomes were similar, but higher than those for the multilamellar liposomes. The basic drugs showed stronger partitioning into negatively charged liposomes than into either neutral liposomes or positively charged liposomes. The membrane fluidity of the immobilized liposomes was modulated by incorporating cholesterol into the liposomal membranes, by changing the acyl chain length and degree of unsaturation of the phospholipids, and by changing the temperature for ILC runs. Our data show that K(LM) obtained using ILC correlated well with those reported by batch studies using free liposomes. It is concluded that negatively charged or cholesterol-containing large unilamellar liposomes are suitable models for the ILC analysis of drug-membrane interactions.
固定化脂质体色谱法（ILC）已被证明是研究或快速筛选药物与膜相互作用的一种有用方法。为了获得用于ILC的合适脂质体膜相，通过抗生物素蛋白-生物素结合将单层脂质体固定在凝胶珠中。15种碱性药物在脂质体柱上的滞留可转化为膜分配系数K（LM）。比较了小单层脂质体、大单层脂质体和多层脂质体对药物-膜分配的影响。小脂质体和大脂质体的K（LM）值相似，但高于多层脂质体。碱性药物在带负电荷的脂质体中的分配比在中性脂质体或带正电荷的脂质体中更强。通过将胆固醇掺入脂质体膜、改变磷脂的酰基链长度和不饱和度以及改变ILC运行的温度来调节固定化脂质体的膜流动性。我们的数据表明，使用ILC获得的K（LM）与使用游离脂质体的批量研究报告的结果相关性良好。结论是，带负电荷或含胆固醇的大单层脂质体是用于药物-膜相互作用ILC分析的合适模型。
