关键词: 细粒棘球蚴, 阿苯达唑, 壳聚糖微球, 脂质体, 昆明小鼠

Abstract: Objective  To observe the therapeutic effect of albendazole chitosan microspheres （ABZ-CS-MPs） on cystic echinococcosis in mice.  Methods  Two hundred male kunming mice were each infected by intraperitoneal inoculation of about 5 000 viable protoscoleces of Echinococcus granulosus. Another 20 mice were kept as blank control. After 12 weeks post infection, the mice were randomly divided into four groups named as infection control group（n=20）, ABZ-CS-MPs group, albendazole liposome（L-ABZ） group, and albendazole tablet group. The latter three treatment groups were then each divided into three subgroups （n=20） by given the dose of 37.5, 75.0, and 150.0 mg/kg for three times per week, respectively. After 12 weeks of treatment, all mice were sacrificed. The weight of hydatid cysts was measured and the inhibition rate were calculated. Mouse liver was observed. The histopathological changes of E. granulosus were observed by microscopy. The concentration of albendazole sulfoxide in plasma and liver tissues was determined by high-performance liquid chromatography.  Results  Compared with the other treatment groups, the turbidity of contained fluid, the consolidation level and calcification level of hydatid cysts in ABZ-CS-MPs group were higher. The average weight of hydatid cysts in each treatment group was lower than that of infection control group［（3.19±2.94） g］（P<0.05）. The cyst weight in 37.5, 75.0, and 150.0 mg/kg ABZ-CS-MPs group［（0.28±0.28）, （0.24±0.22）, and （0.20±0.19） g, respectively］ was lower than that of albendazole tablet groups ［（0.77±0.74）, （0.55±0.42）, （0.76±0.35） g］（P<0.05）. Among the same dosage groups, the inhibition rate in ABZ-CS-MPs group（from low to high dosage sub-group: 91.1%, 92.6%, and 93.7%, respectively） was highest. In 75.0 mg/kg ABZ-CS-MPs group, there were 15 mice with classⅠ（degeneration） and Ⅱ（necrosis） pathological changes of E. granulosus hydatid. The number of mice with class Ⅰ and Ⅱ pathological changes in each dosage ABZ-CS-MPs sub-group and L-ABZ sub-group was more than that of albendazole tablet group（P<0.05）. Plasma concentration of albendazole sulfoxide in 75.0 and 150.0 mg/kg ABZ-CS-MPs sub-groups ［（0.83±0.39）, （0.80±0.5） μg/ml］ were higher than that of L-ABZ sub-groups［（0.34±0.03）, （0.43±0.15） μg/ml］ and albendazole tablet sub-groups ［（0.31±0.02）, （0.40±0.10） μg/ml］（P<0.05）. Compared with 37.5, 75.0, and 150.0 mg/kg albendazole tablet sub-groups ［（0.04±0.02）, （0.07±0.04）, （0.04±0.0） μg/g］, the albendazole sulfoxide concentration in liver tissue was higher in ABZ-CS-MPs sub-groups ［（0.33±0.06）, （0.45±0.31）, （0.50±0.30） μg/g］（P<0.05）. In 37.5 mg/kg dosage sub-group, the albendazole sulfoxide concentration in liver tissue in ABZ-CS-MPs group was higher than that of L-ABZ group ［（0.14±0.19） μg/g］（P<0.05）.  Conclusion  ABZ-CS-MPs can reduce the weight of hydatid cyst and increase the concentration of albendazole sulfoxide in plasma and liver tissue of mice.

Key words: Echinococcus granulosus, Albendazole, Chitosan microsphere, Liposome, Kunming mouse