口服和注射阿苯达唑脂质体治疗小鼠肝及腹腔细粒棘球蚴感染的比较观察

Comparative Observation on Efficacy of Liposomal Albendazole Against Infection with Echinococcus granulosus by Oral and Introperitoneal Injection

为观察阿苯达唑脂质体 (L- ABZ)经腹腔注射治疗感染细粒棘球蚴 (E.g)的疗效并比较其与口服阿苯达唑脂质体及单纯用阿苯达唑 (ABZ)治疗细粒棘球蚴病的疗效 ,选用 NIH小鼠 (2 0 g± 1g) ,阿苯达唑脂质体采用中和法 ,按阿苯达唑 37.5 mg/ kg·次、75 mg/ kg·次及 15 0 mg/ kg·次 ,按 2 0 g小鼠一次用量各 0 .2 m L 配制 ,单用阿苯达唑用花生油助溶剂也按上述方法配制成 3种不同浓度每次每只小鼠用 0 .2 m L,原头节取自绵羊肝脏 E.g内囊 ,实验动物分为对照组、口服单纯阿苯达唑组 (Po- ABZ)、口服阿苯达唑脂质体组 (Po- L - ABZ)和腹腔注射阿苯达唑脂质体组 (Ip- L - ABZ) ,后 3组按阿苯达唑 37.5 mg/ kg·次、75 mg/ kg·次及 15 0 mg/ kg·次依次又各分为 3小组 ,与对照组共计 10组 ,NIH小鼠腹腔接种感染 12 W后开始用药 (对照组给予同容量蒸馏水 )每次 0 .2 m L ,用药 3次 / W(每周一、三、五给药 ) ,10 W后解剖 ,观察指标为 :(1)大体形态 ;(2 )囊湿重 (减重率 ) ;(3)病理组织学变化 ;(4 )测定血液和肝脏中的 ABZ及其代谢产物砜 (ABZSN)和亚砜 (ABZSX)的浓度 ,并进行疗效的综合评价。结果显示 :(1)口服阿苯达唑脂质体治疗感染 E.g小鼠的效果优于单纯口服阿苯达唑 ;(2 )腹腔注射阿苯达唑脂质体治疗效果?

Evaluation of the effect for the treatment of NIH mice with Echinococcus granulosus (E.g) infection was made using liposome entrapped albendazole (L ABZ) by oral and introperitoneal injection in comparison with free ABZ orally. total of 250 mice were introperitoneally infected with E.g and developed for 12 week. The 200 remained mice were then randomly divided into 4 groups as follows:(1)Oral administration of distilled water as a group, (2)Po ABZ group: mice were given free ABZ orally;(3) (Po L ABZ)group: mice were orally administered by L ABZ;(4) (Ip L ABZ)group: mice were introperitoneally infected by L ABZ .The above three treated groups were then divided into three subgroups by given the dose of 37.5mg/kg,75mg/kg and 150mg/kg for three times per week. All the animals were treated for a total of 10 week and then sacrificed for drag efficacy assessment, four judging criteria were adopted as that.(1) The ultrastructural changes, (2) Reduction rate of cyst weight,(3) Histopathological changes of cyst both in microscopy and electronic microscopy and (4) Concentrations of ABZ and its main metabolities, albendazole sulphoxide(ABZSX) and albendazole sulphone distribution. Both oral and injecting administration by L ABZ showed better effect than that by free ABZ. The E.g cyst reduction rates were 84.9%,86.4%,89.2% in the Po ABZ groups; 85.4%, 91.9%, 92.6% in the Po L ABZ groups;92.2%,94.8%,96.4% in the Ip L ABZ groups, respectively. The histopathological and ultrastruetral changes of E.g tissues showed more serious changes in both Po L ABZ groups and IP L ABZ group than that in Po ABZ group, and moreover, the changes in IP L ABZ against E.g by peritineal injection had more effect than that in oral administration group. The statistical significance was found among the different dosage by intropefitoneal injection. The drug concentration were measured by RP HPLC in blood and liver tissues which showed higher levels in the PO L ABZ group and in the IP L ABZ group than that in Po ABZ group. It could be concluded that, 1.L ABZ played a role in targeting and increasing drug absorbtion and distribution to the liver tissues, especially by way of injection. 2.The change of the cyst weight reduction rate and the histopathological change and the concentration of ABZSX,ABZSN and ABZ in blood and liver, convincingly confirmed the antihydatid effect by L ABZ formulation against E.g in mice. In addition, pertoneal injection had more effect than by oraladministration. 3. There were different effects among the three doses with Ip L ABZ which initially supported (37.5 mg) dose application and further experiments were needed in future study.$$$$