| Objective:This study aimed at comparing the efficacy of chemotherapy employing Albendazole Chitosan Microsphere (ABZ-CS-MPs), Liposome-Albendazole(L-ABZ) and Albendazole Tablet (ABZ-T) for secondary established intraperitoneal infections of Echinococcus multilocularis (E. multilocularis) Metacestodes in an experimental murine model, and evaluate the therapeutic effect of ABZ-CS-MPs in mice infected with Echinococcus multilocularis, in order to improve the chemotherapeutic efficacy to provide experimental bases.Methods:220 Male Kunming mice infected with E. m Metacestodes were prepared as secondary alveolar echinococcosis murine model by injected protoscolices intraperitoneally. Mice infected with E. m Metacestodes for 12 weeks and administrated with three ABZ formulations, namely ABZ-CS-MPs, Liposome-Albendazole (L-ABZ), Albendazole tablet (ABZ-T) and infection control, respectively(besides, add a control group). Each above ABZ formulation was given orally at three dosages of 37.5mg/kg,75mg/kg, and 150mg/kg, respectively,Model control group were administrated with saline. It was administrated three times a week for consecutive 12 weeks post infection.20 mice was prepared for every dosage subgroups. After administrating the above drugs, following criteria were monitored as evaluating the therapeutic efficacy. (1) observe morphological changes of E. multilocularis in mice; (2) parasite biomass was weighed and calculate parasite inhibitory rate; (3) observation of histopathological changes of the E.m vesicles; (4) observe ultrastructural changes of the E.m tissue by Transmission electron microscopy (TEM); (5) Plasma levels of ABZ-SX were estimated by high performance liquid chromatography (HPLC).Results:It was observed that the sizes of liver surface vesicles were were shrunken significantly in mice with drug treatments when compared with untreated controls, particularly, the metastasis of hydatid vesicles in mice administrated with ABZ-CS-MPs and L-ABZ were significantly reduced rather than those mice administrated with ABZ-T. The color of most lesions was changed to yellow or cloudy white, texture was changed to hardened and calcified small vesicles were seen on the surface of the liver. Cyst wet weight in mice administrated orally for 37.5mg/kg,75mg/kg,150mg/kg dosage subgroups were:ABZ-CS-MPs:(0.176±0.033,0.123±0.016,0.085±0.029) g; L-ABZ:(0.156±0.020,0.147 ±0.026,0.137±0.026) g; ABZ-T:(0.496±0.095,0.433±0.069,0.337±0.063) g; separately. The difference was statistically significant when compared those 3 ABZ formulations treated group with infection control group (1.565±0.020)g, (P<0.05). The inhibitory rates up to 92.13% and 94.56% in the 75mg/kg and 150mg/kg subgroups in mice treated with ABZ-CS-MPs and higher than those L-ABZ treated group (90.58%,91.23%) and ABZ-T treated group (72.32%,78.46%) separately. Histology revealed that there was different level of degeneration, necrosis in mice treated with ABZ-CS-MPs or L-ABZ. Germinal layer and laminated layer was severely broken, characteristic structure of E.m Metacestodes was disappeared. Meanwhile, ABZ-SX has attained a significantly higher plasma levels in mice treated with ABZ-CS-MPs or L-ABZ. ABZ-SX plasma concentration in each dosage subgroups for 37.5mg/kg,75mg/kg,150mg/kg were:ABZ-CS-MPs:ABZ-CS-MPs:(0.6785, 1.1011,1.4035)μg/ml; L-ABZ:(1.0410,0.8587,1.0275) μg/ml; ABZ-T:(0.3141, 0.4307,0.5409)μg/ml; In all treated groups, ABZ-SX plasma concentration shows highest level with the treatment of ABZ-CS-MPs in the 75mg/kg and 150mg/kg dosage subgroups, the difference was statistically significant compared with mice treated with ABZ-T(P<0.01).Conclusion:Three ABZ dosage forms had different extent of suppressive effect on the growth of E. m Metacestodes, in particular, ABZ-CS-MPs had promoted the intestinal absorption of ABZ effectively and further had increased the concentration of ABZ-SX as a main metabolite of ABZ in plasma, promises to be a new dosage form for the treatment of echinococcosis. |
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