莪术油包合物复合磷脂脂质体的药剂学性质与急性毒性研究.doc

莪术油包合物复合磷脂脂质体的药剂学性质与急性毒性研究

[摘要]  目的：比较不同磷脂组成对莪术油包合物脂质体药剂学性质以及急性毒性的影响。方法：采用饱和水溶液法制备莪术油-羟丙基--β-环糊精包合物，乙醇注入法制备双分子层和内水相同时载药的莪术油包合物复合磷脂脂质体。比较了莪术油包合物脂质体（主要磷脂材料为大豆磷脂SPC）与莪术油包合物复合磷脂脂质体（主要磷脂材料为氢化大豆磷脂HSPC与SPC的混合物，两者重量比为1:9）的包封率、粒径、电位、释放度、泄漏率等药剂学性质。比较了莪术油溶液、莪术油环糊精包合物以及两种莪术油包合物脂质体的急性毒性。结果：莪术油包合物复合磷脂脂质体的包封率、粒径、电位与包合物脂质体相当，但释放度和泄漏率实验结果表明其稳定性显著高于莪术油包合物脂质体。莪术油溶液、莪术油环糊精包合物，莪术油包合物脂质体和莪术油包合物复合磷脂脂质体静脉注射后的LD50分别为207.87、153.31、269.13和327.30mg/kg。结论：复合磷脂脂质体技术可以显著提高莪术油包合物脂质体的稳定性和安全性。
[关键词] 莪术油；包合物脂质体；稳定性；氢化大豆磷脂；大豆磷脂；急性毒性

Investigation on pharmaceutical property and acute toxicity of zedoary turmeric oil liposomes composed of HSPC and SPC using cyclodextrin complex

  [Abstract]  Objective: To compare the effect of phospholipids composition on pharmaceutical characteristics and saftey of liposomes containing zedoary turmeric oil (ZTO) and ZTO hydroxypropyl-β-cyclodextrin (HP-β-CD) complex. Methods: ZTO HP-β-CD complex was prepared and obtained by freeze-drying technique. The ZTO liposomes were prepared by ethanol injection method to realize double loading of ZTO in liposomes. To determine the entrapment efficiency of ZTO liposomes, liposome suspension was passed through a Sephadex G-50 column equilibrated with PBS to separate liposomal and free ZTO.  Pharmaceutical characteristics such as entrapment efficiency, size, zata potential, release profiles and stability were determined and compared between ZTO complex liposomes composed of soybean phosphatidylcholine (SPC) or the mixture of hydrogenated soybean phosphatidylcholine (HSPC) and SPC (1:9, w/w). Acute toxicity of ZTO solution, complex and complex liposomes was compared. Results: ZTO complex liposomes composed of SPC had the similar entrapment efficiency, size and zeta potential compared to the corresponding liposomes composed of HSPC and SPC. But the results of release profiles and leakage experiments revealed that the stability of ZTO complex liposomes composed of HSPC and SPC was significantly higher than that of SPC liposomes. The LD50 values of ZTO solution, complex, complex liposomes composed of SPC and complex liposomes composed of both HSPC and SPC were 207.87, 153.31, 269.13 and 327.30 mg/kg following intravenous administration, respectively. Conclusion: As the carrier of ZTO, complex liposomes composed of both HSPC and SPC possess good stability and safety compared with complex liposomes composed of SPC.
  [Key words]   Zedoary turmeric oil (ZTO); complex liposomes; stability; hydrogenated soybean phosphatidylcholine (HSPC); soybean phosphatidylcholine (SPC); acute toxicity