转铁蛋白顺铂长循环脂质体的制备及质量研究

目的研制转铁蛋白（transferrin,Tf）修饰顺铂长循环脂质体（Tf-PEG-CDDP）,考察其物理性状及体外释放特性。方法采用薄膜分散-超声法制备空白脂质体,硫酸铵梯度法包载顺铂,通过膜材DSPE-PEG_（2000）-MAL的末端活性基团连接转铁蛋白制备Tf-PEG-CDDP;用超滤法分离顺铂脂质体和游离顺铂,紫外可见光分光光度计测定Tf-PEG-CDDP的包封率;采用激光散射粒径分析仪测定粒径和透射电镜观察其性状;透析法检测顺铂脂质体体外缓释能力。结果 Tf-PEG-CDDP呈圆形囊泡样结构,大小略不均一,平均粒径为200 nm,包封率平均为（78.222±5.4086）%,稳定性尚可。体外释放实验示Tf-PEG-CDDP有明显优于CDDP的缓释能力。结论 Tf-PEG-CDDP具有缓释能力,是一种有效的顺铂靶向制剂。

Preparation of cisplatin-loaded long-circulating liposomes modified with transferrin

Objective To develop cisplatin-loaded long-circulating liposomes modified with transferrin（Tf-PEG-CDDP）.Methods The blank liposomes were prepared by thin film dispersion-ultrasound method and cisplatin was packaged by ammonium sulfate gradient method.Tf-PEG-CDDP was prepared by binding transferrin to maleimide terminal of DSPE-PEG₂₀₀₀-MAL.Free cisplatin and cisplatin liposomes were separated by ultrafiltration.The encapsulation efficiency of Tf-PEG-CDDP was determined with UV-Vis spectrophotometer.The size was detected by laser scattering particle size analyzer and the physical properties were observed by transmission electron microscopy.Dialysis was used to study the release of cisplatin in vitro.Results Electron microscopy demonstrated that Tf-PEG-CDDP was round vesicle-like structure and the size was slightly uneven with an average particle size of 200 nm.The mean cisplatin encapsulation efficiency of liposomes was（78.222±5.4086）%.In vitro release test showed that the slow-release property of Tf-PEG-CDDP was significantly better than that of CDDP.Conclusion The cisplatin-loaded liposomes modified with transferrin Tf-PEG-CDDP has been successfully developed with a satisfactory slow-release property.