齐墩果酸冻干脂质体的制备及对四氯化碳致小鼠急性肝损伤的保护作用

Preparation of Lyophilized Oleanolic Acid Liposomes and Protective Effect on CCl_4-Induced Acute Hepatic Injury in Mice

采用乙醇注入法制备齐墩果酸冻干脂质体,再用自制的三甲基壳聚糖进行表面修饰。通过比较冻干品外观、冻干前后理化性质变化,筛选最优冻干工艺、冻干保护剂种类与用量。结果表明,以6%海藻糖为冻干保护剂,经-80℃速冻6 h,冷冻干燥30 h,可得到外观良好、易重建的冻干脂质体。冻干前后药物包封率为(96.8±1.7)%和(97.1±0.9)%,平均粒径为(164.0±4.2)和(195.5±5.9)nm,ζ电位为(23.8±0.2)和(20.3±1.1)mV。采用四氯化碳致小鼠急性肝损伤模型考察制品对生化指标的改善作用。与模型组相比,本品可明显降低小鼠血清丙氨酸转氨酶、门冬氨酸转氨酶和肝组织丙二醛水平,对急性肝损伤的保护作用明显。

The oleanolic acid liposomes were prepared by ethanol injection method, followed by surface modification with self-synthesized trimethyl chitosan. Through comparing of appearances and physicochemical properties of the liposomes before and after lyophilization, the lyophilized process parameters, kinds and amounts of lyoprotectants were optimized. The results showed that lyophilized liposomes with good appearance and reconstitution were obtained by using 6 % trehalose as lyoprotectant, pre-freezing at -80 ℃ for 6 h and lyophilizing for 30 h. The encapsulation efficiency, particle size and ζ potential of the liposomes before and after lyophilization were （96.8±1.7） % and （97.1±0.9） %, （164.0±4.2） and （195.5±5.9）nm, （23.8±0.2） and （20.3±1.1） mV, respectively. The improvement of the product on biochemical markers of mice with acute hepatic injury induced by CCl4 was investigated. Compared with model group, the liposomes could significantly decrease the ALT and AST activities in serum and malondialdehyde level in liver, showing promising protective efficacy on liver injury.