Vali Amir Masoud, Toliyat Taiebeh, Shafaghi Bijan, Dadashzadeh Simin
Department of Pharmaceutics, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.
Drug Dev Ind Pharm. 2008 Jan;34(1):10-23. doi: 10.1080/03639040701385055.
This study reports the development of liposomal system for a potent antitumor drug, topotecan. To achieve this goal conventional and PEGylated liposomes were prepared according to a factorial design by hydration method followed by extrusion. Parameters such as type of lipid, percentage of cholesterol, percentage of phosphatidylglycerols, percentage of polyethylene glycol (PEG)-lipids, and drug to lipid molar ratio were considered as important factors for the optimizing the entrapment and retention of topotecan inside the liposomes. The size and zeta-potential of the PEGylated and conventional liposomes were measured by particle size analyzer and zeta-potentiometer, respectively. The stability and release characteristics of PEGylated liposome loaded topotecan were compared with conventional liposomes and free topotecan. The optimized PEGylated [distearoyl phosphatidylcholine (DSPC)/cholesterol/ distearoyl phosphatidylglycerol (DSPG)/ distearoyl phosphatidylethanolamine-PEG(2000) (DSPE-PEG(2000)); 7:7:3:1.28] and related conventional [DSPC/cholesterol/DSPG; 7:7:3] liposomes showed a narrow size distribution with a polydipersity index of 0.15 and 0.10, an average diameter of 103.0 +/- 13.1 and 95.2 +/- 11.10 nm, and with drug loading of 11.44 and 6.21%, respectively. Zeta-potential was -10 +/- 2.3 and -22 +/- 2.8 mV for PEGylated and conventional liposomes, respectively. The results of stability evaluation showed that the lactone ring of topotecan was notably preserved upon liposome encapsulation. PEGylated liposomes containing topotecan showed a significant decrease (P < 0.001) in release rate in comparison with conventional leptosomes. These results indicate the suitability of PEGylated liposomes in controlling topotecan release. The prepared liposomes (especially PEGylated liposomes) as those described here may be clinically useful to stabilize and deliver topotecan for the treatment of cancer.
本研究报道了一种用于强效抗肿瘤药物拓扑替康的脂质体系统的研发。为实现这一目标，按照析因设计通过水化法随后进行挤压制备了常规脂质体和聚乙二醇化脂质体。脂质类型、胆固醇百分比、磷脂酰甘油百分比、聚乙二醇（PEG）-脂质百分比以及药物与脂质的摩尔比等参数被视为优化拓扑替康在脂质体内包封和保留的重要因素。分别通过粒度分析仪和ζ电位仪测量了聚乙二醇化脂质体和常规脂质体的大小和ζ电位。将负载拓扑替康聚乙二醇化脂质体的稳定性和释放特性与常规脂质体和游离拓扑替康进行了比较。优化后的聚乙二醇化脂质体[二硬脂酰磷脂酰胆碱（DSPC）/胆固醇/二硬脂酰磷脂酰甘油（DSPG）/二硬脂酰磷脂酰乙醇胺-PEG（2000）（DSPE-PEG（2000））；7:7:3:1.28]和相关常规脂质体[DSPC/胆固醇/DSPG；7:7:3]显示出窄的粒径分布，多分散指数分别为0.15和0.10，平均直径分别为103.0±13.1和95.2±11.10nm，药物载量分别为11.44%和6.21%。聚乙二醇化脂质体和常规脂质体的ζ电位分别为-10±2.3和-22±2.8mV。稳定性评估结果表明，拓扑替康的内酯环在脂质体包封后得到了显著保留。与常规脂质体相比，含有拓扑替康的聚乙二醇化脂质体的释放速率显著降低（P<0.001）。这些结果表明聚乙二醇化脂质体适用于控制拓扑替康的释放。本文所述制备的脂质体（尤其是聚乙二醇化脂质体）在稳定和递送拓扑替康用于癌症治疗方面可能具有临床应用价值。
