奥沙利铂脂质体的制备及体外释药研究

Preparation of oxaliplatin liposome and in vitro drug-release

目的制备一种包封率较高的奥沙利铂脂质体,并考察该脂质体的体外性质。方法采用多种方法制备奥沙利铂脂质体,通过单因素试验和正交试验最终确定脂质体处方。采用高效液相色谱法检测脂质体包封率,Zeta Plus激光粒度分析仪测定脂质体粒径。同时,采用高效液相色谱法、原子吸收光谱法两种方法考察了该脂质体的体外释放情况。结果与薄膜分散法和p H梯度法相比,通过逆相蒸发法制备得到的了奥沙利铂脂质体包封率更高;在此基础上进行的处方筛选试验确定了最优处方工艺为药脂比1∶7.5,胆磷比1∶2,超声功率195 W,超声时间3 min;体外释放试验结果表明,通过高效液相色谱法和原子吸收光谱法测定的奥沙利铂脂质体24 h的累计释放率分别为25.0%和33.6%。结论通过逆相蒸发法制备得到的奥沙利铂脂质体包封率高,且具有较高的稳定性和一定的缓释作用。

Objective To prepare oxaliplatin liposomes with high encapsulation efficiency,and to investigate the in vitro properties of them. Methods Compare oxaliplatin liposomes prepared by several methods,and determine the best pre-scription through the single factor experiment and orthogonal experiment. In the experiment HPLC was used to determine the encapsulation efficiency,and Zetaplus Laser Particle Size Analyzer was used to determine the particle size and zeta potential of liposomes. In addition,both HPLC method and AAS method was used to investigate the in vitro release of the liposomes. Results Compared with thin - film dispersion method and pH gradient method,liposomes prepared by reverse phase evap-oration method presented higher encapsulation efficiency. The best prescription determined by formulation screening was:the ratio of drug to lipid with 1∶7. 5,the ratio of SPC to CH with 2∶1,the ultrasonic power with 195 W and the ultrasonic time with 3 min. In vitro drug release study indicated that the accumulative releasing degree of oxaliplatin liposomes in 24 h was 25. 0% ,determined by HPLC,and 33. 6% ,determined by AAS. Conclusion Liposomes prepared by the reverse phase e-vaporation method were stable enough and assume high encapsulation efficiency and showed the capability of sustained - re-leasing.