【摘要】 目的　观察多种药物载体 [大分子物 (Macrosol)、脂质前体 (Pre- liposome)、脂质体 (liposome) ]与 ABZ结合后 ,ABZ的生物利用度和抗棘球蚴病的效果。　方法　选用 90只健康长爪沙鼠 ,随机分为 9组 ,每组 10只。腹腔接种泡球蚴组织 (E.m) ,建立动物模型。接种 6周后开始给药 ,治疗组 ABZ均按 5 0 mg/ kg剂量给药 ,对照组每只长爪沙鼠经口服或腹腔注射 0 .2 ml生理盐水。每周一、三、五 ,连续 6周。末次给药后 4 h将动物处死 ,取血、肝、E.m组织。观察指标 :1) E.m湿重及减重率 ;2 ) E.m组织头节阳性率 ,再观察病理组织学改变 ;3) HPL C测定血、肝、囊内的 ABZ及其主要代谢产物ABZSX和 ABZSN的浓度。　结果　新剂型 ABZ组 (总体 ) E.m组织的减重率与 ABZ片剂粉末组相比 ,差异有显著性(P<0 .0 5 )。病理切片头节的阳性率与对照组相比差异有显著性。超微结构的改变与其相符合。代谢产物 ABZSX和ABZSN的血药浓度分别是 :1) ABZSN的药物浓度 :L- ABZ口服组 :血浆中为 (1.0 14± 0 .2 39) μg/ g,肝脏中为 (0 .0 36±0 .0 0 7) μg/ g,E.m组织中为 (0 .0 31± 0 .0 0 9) μg/ g;L- ABZ注射组 :血浆中为 (2 .4 2 3± 1.0 70 ) μg/ g,肝脏中为 (0 .6 88±0 .0 0 8) μg/ g,E.m组织中为 (0 .0 4 9± 0 .0 0 8)更多还原

【Abstract】 Objective To observe the efficacy of the new drug deliver system (liposome, pre-liposome, macrosol) enclosed albendazole(ABZ) to against the Echinococcus multilocularis(E.m) infection in Gerbils. Methods 90 gerbils were randomly divided into 9 groups and 10 gerbils in each group. 8 groups were introperitoneally infected with E.m tissues and protoscoleces for 6 weeks. These gerbils were treated by the same dosage of ABZ 50 mg/kg and, with different formulation as follows: 1) P-ABZ group: gerbils were orally given ABZ powder; 2) L-ABZ group: gerbils were orally administered by L-ABZ; 3) L-ABZ group: gerbils were introperitoneally injected by L-ABZ; 4) P-L-ABZ group: gerbils were orally treated by P-L-ABZ; 5) M-ABZ group: gerbils were orally took M-ABZ; 6) 0.9%NS group: gerbils were orally administered 0.9%NS for 2 ml/each; 7) 0.9%NS group: gerbils were introperitoneally injected 0.9%NS 2 ml/each; All gerbils treated 3 times a week, totally 6 weeks. Remained one group as a control group, no infection and no treated. Four criteria for different drug formulation efficacy were employed: 1) Wet weight and reduction rate of E.m tissues; 2) histopathological and ultrastructural changes; 3) Concentrations of ABZ and it’s main metabolites, ABZ sulfoxide and ABZ sulfone in plasma, liver and E.m tissues. Results 1) Average wet weight of E.m tissues in treated group was (3.90±2.25) g and, (8.82±4.11) g in control group (P<0.05). The reduction rate of wet weight of E.m tissues showed as follows: 73.8% in P-L-ABZ(oral) group,the others one by one is 59.3% in L-ABZ (oral) group, 55.4% in M-ABZ (oral) group, 50.3% in L-ABZ (injection) group, 40.1% in P-ABZ (oral) group; 2) Histopathological and ultrastructural changes were obviously in treated group compare with control group. 3. Concentration of ABZ sulfoxide and ABZ sulfone in plasma, liver and E.m tissues 4 hour after last dosage are much high than control group(P<0.05). Conclusion The formulation of pre-liposome and macrosol are effective drug deliver system, could increase the concentration of ABZSX and ABZSN in plasma, liver and E.m tissues, reduced E.m biomass and protocolexes by enclosed ABZ.更多还原