羟基喜 树 碱在脂质体 / 水相中分配的影响因素研究

 目的 检测羟基喜树碱在脂质体 / 水相中的分配，考察影响分配的因素，探讨羟基喜树碱与脂质体膜的结合活化能。 方法 采取平衡透析法测定羟基喜树碱在脂质体 / 水相中的分配系数，考察了脂质体膜（磷脂种类、磷脂与胆固醇比例）、外界溶液 pH 值及离子强度对药物在脂质体 / 水相中分配的影响；根据表观分布平衡常数的自然对数 (ln<>K_app) 与绝对温度倒数 (1/<>T) 的直线斜率 ( - △ <> G /<>R) ，计算药物分子和脂质体膜之间的结合活化能。 结果 随着脂质体膜的刚性增强，药物在脂质体膜中的分配降低；随着溶液中碱性增强 (pH > 4.0) ，药物在脂质体膜中分配逐渐降低；随着溶液中离子强度的增强，药物在脂质体膜中分配提高。药物与脂质体膜的结合活化能（△ <> G ）为 - 11.698 kJ·mol^-1 。 结论 羟基喜树碱在脂质体中的分配受磷脂膜、溶液 pH 值、离子强度等的影响，药物与脂质体膜的结合为放热反应。

Study on Partition of Hydroxycamptothecin in the Phases of Liposome and Water

OBJECTIVE To determine the partition of hydroxycamptothecin in the phases of liposome and water and to evaluate the influence on the partition coefficients and binding Gibbs energy between the molecules of drug and water. METHODS ■Equilibrium dialysis technique was used to study the liposome/water partition coefficients of drug. The properties of liposome membrane (lipid species and the ratios of cholesterol), pH and ionic strength of medium were studied. The binding Gibbs energy (ΔG) was calculated according to the slope rate of the curve of lnKapp against 1/T. RESULTS The partition of drug in the phases of liposome and water decreased with the increase of membrane rigidity and pH of medium (when pH 4.0), while ionic strength showed the opposite effect on the partition. The binding Gibbs energy (ΔG) of the molecules of drug and liposome membrane was -11.698 kJ·mol-1. CONCLUSION The partition of hydroxycamptothecin in liposome and water may be influenced by the liposome membrane, pH and ionic strength of the medium.