莪術油包合物復合磷脂脂質體的藥劑學性質與急性毒性研究

[摘要]  目的：比較不同磷脂組成對莪術油包合物脂質體藥劑學性質以及急性毒性的影響。方法：采用飽和水溶液法制備莪術油-羥丙基--β-環(huán)糊精包合物，乙醇注入法制備雙分子層和內水相同時載藥的莪術油包合物復合磷脂脂質體。比較了莪術油包合物脂質體（主要磷脂材料為大豆磷脂SPC）與莪術油包合物復合磷脂脂質體（主要磷脂材料為氫化大豆磷脂HSPC與SPC的混合物，兩者重量比為1:9）的包封率、粒徑、電位、釋放度、泄漏率等藥劑學性質。比較了莪術油溶液、莪術油環(huán)糊精包合物以及兩種莪術油包合物脂質體的急性毒性。結果：莪術油包合物復合磷脂脂質體的包封率、粒徑、電位與包合物脂質體相當，但釋放度和泄漏率實驗結果表明其穩(wěn)定性顯著高于莪術油包合物脂質體。莪術油溶液、莪術油環(huán)糊精包合物，莪術油包合物脂質體和莪術油包合物復合磷脂脂質體靜脈注射后的LD50分別為207.87、153.31、269.13和327.30mg/kg。結論：復合磷脂脂質體技術可以顯著提高莪術油包合物脂質體的穩(wěn)定性和安全性。
[關鍵詞] 莪術油；包合物脂質體；穩(wěn)定性；氫化大豆磷脂；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