三磷酸腺苷二钠脂质体的制备及其对心肌缺血小鼠组织能量状态的影响

Preparation of ATP-2Na loaded liposome and its effect on tissues energy state in myocardial ischemic mice

采用离子对复合物方法制备三磷酸腺苷二钠(ATP-2Na)脂质体以提高包封率,并考察其对心肌缺血小鼠组织能量状态的影响。ATP-2Na与十六烷基三甲基溴化铵(hexadecyl trimethyl ammonium bromide,HTAB)形成离子对复合物后用乙醇注入法制备脂质体,测定载药脂质体的粒径、表面电位等理化参数;以ATP-2Na溶液为对照,测定给药后心肌缺血小鼠血液及各组织中ATP浓度,评价脂质体对提高心肌缺血小鼠组织能量状态的作用。结果表明,ATP-2Na脂质体的平均粒径为(144.0±2.7)nm,表面电位为(+16.2±1.6)mV,包封率为(85.02±2.31)%,体外释药遵循Weibull方程。ATP-2Na脂质体与ATP-2Na溶液相比显著地提高了心肌缺血小鼠血液中的ATP浓度;ATP-2Na脂质体与生理盐水相比显著提高了缺血心肌及肝组织中的ATP浓度,而游离ATP-2Na却无此效果。表明ATP-2Na脂质体对提高心肌缺血动物的组织能量状态有一定的应用价值。

The aim of this study is to improve liposome encapsulation efficiency of water soluble drug ATP-2Na with hydrophobic ion pairing method, and evaluate its effect on tissues energy state in myocardial ischemia mice. Ion pair complex of ATP-2Na with HTAB was prepared first; then the liposomes were prepared by ethanol injection method. The size and zeta potential of ATP-2Na liposome were investigated. Its effect on tissues energy state in myocardium ischemia mice was evaluated by detecting ATP-2Na concentration in tissues and blood after injection in comparison to ATP-2Na solution. The diameters and zeta potential of ATP-2Na liposomes were （144.0 ± 2.7） nm and （＋16.2 ± 1.6） mV, respectively. The encapsulation efficiency was （85.02 ± 2.31） %. The in vitro drug release pattern from liposomes matches with Weibull equation. Compared with ATP-2Na solution, ATP-2Na liposome increased the ATP concentration of blood in myocardial ischemic mice very significantly; compared with blank, ATP-2Na liposome increased ATP content of myocardium and liver in myocaridal ischemic mice significantly, but ATP-2Na solution didn＇t show this effect. ATP-2Na liposome might have an advantage in improving tissue energy state on myocaridal ischemic animals.