不同磷脂组成的莪术油包合物脂质体的药剂学性质与急性毒性研究

Effect of phospholipid composition on pharmaceutical property and acute toxicity of liposomes entrapped zedoary turmeric oil and its inclusion

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-环糊精包合物并且冷冻干燥得到固体,乙醇注入法制备莪术油包合物脂质体。比较了使用大豆磷脂(SPC)或使用复合磷脂组成[氢化大豆磷脂(HSPC)+大豆磷脂(SPC)]对制得的莪术油包合物脂质体的药剂学性质(包封率、粒径、电位、释放度、泄漏率等)的影响。并且进一步比较了莪术油溶液、莪术油包合物以及两种不同磷脂组成莪术油包合物脂质体的急性毒性。结果添加10%HSPC对莪术油包合物脂质体的包封率、粒径、电位等没有影响,但释放度和泄漏率实验结果表明莪术油HSPC+SPC包合物脂质体的稳定性显著高于莪术油包合物SPC脂质体。莪术油溶液、莪术油环包合物,莪术油包合物SPC脂质体和莪术油包合物HSPC+SPC脂质体静脉注射后的LD50分别为207.87、153.31、269.13和327.30 mg/kg。结论应用复合磷脂组成(HSPC+SPC)可以显著提高莪术油包合物脂质体的稳定性和安全性。

AIM To compare the effect of phospholipid composition on pharmaceutical characteristics and a- cute toxicity of liposomes containing zedoary turmeric oil （ZTO） and ZTO hydroxypropyl-β-cyclodextrin inclusion complex （ZTO-CD）. METHODS ZTO-CD was prepared by saturated water solution method and obtained by freeze-drying technique. The liposomes were prepared by ethanol injection method and used to encapsulate ZTO-CD into liposomes. Pharmaceutical characteristics such as entrapment efficiency, size, zeta potential, release profiles and stability were determined and compared between ZTO-CD-loaded liposomes with different phospholipid compo- sition （ SPC or HSPC ＋ SPC）. Acute toxicity of ZTO solution, ZTO-CD and ZTO-CD-loaded liposomes with different phospholipid composition was also compared. RESULTS ZTO-CD-loaded HSPC ＋ SPC liposomes had the similar entrapment efficiency, size and zeta potential compared with the corresponding SPC liposomes. But the results of release profiles and leakage experiments revealed that the stability of ZTO-CD-loaded HSPC ＋ SPC liposomes was significantly higher than that of SPC lipsomes. The LDs0 values of ZTO solution, ZTO-CD, ZTO-CD- loaded SPC liposomes and ZTO-CD-loaded HSPC ＋ SPC liposomes were 207.87, 153.31,269.13 and 327.30 mg/ kg following intravenous administration, respectively. CONCLUSION As to the carrier of ZTO, liposomes com- posed of both HSPC and SPC possess good stability and safety compared with conventional SPC liDosomes.