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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(lnKapp)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-11.698kJ·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。
Objective To detect the distribution of hydroxycamptothecin in liposome / aqueous phase, investigate the factors affecting the distribution and explore the binding activation energy of hydroxycamptothecin with liposome membrane. Methods The partition coefficient of hydroxycamptothecin in liposome / aqueous phase was determined by equilibrium dialysis method. The effects of liposome membrane (phospholipid type, phospholipid and cholesterol ratio), external solution pH value and ionic strength on lipid distribution The distribution of drug molecules and liposomes was calculated based on the linear slope (- △ G / R) of natural logarithm (lnKapp) of apparent equilibrium constant and absolute reciprocal of temperature (1 / T) The combination of activation energy. Results As the rigidity of the liposome membrane increased, the distribution of the drug decreased in the liposome membrane. The distribution of the drug in the liposome membrane gradually decreased with the increase of pH in the solution (pH> 4.0) Increased ionic strength, drug distribution in the liposome membrane increased. The binding activation energy (△ G) of drug and liposome membrane was -11.698kJ · mol-1. Conclusion The distribution of hydroxycamptothecin in liposomes is affected by phospholipid membrane, solution pH, ionic strength and the like. The combination of drug and liposome membrane is exothermic.