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PLoS Negl Trop Dis ; 9(9): e0003950, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26352932

RESUMEN

This study aimed to investigate the pharmacology and anti-parasitic efficacy of albendazole-chitosan microspheres (ABZ-CS-MPs) for established intraperitoneal infections of Echinococcus multilocularis metacestodes in an experimental murine model. Male outbred Kunming mice infected with E. multilocularis Metacestodes were administered with three ABZ formulations, namely, ABZ-CS-MPs, Liposome-Albendazole (L-ABZ), and albendazole tablet (ABZ-T). Each of the ABZ formulations was given orally at three different doses of 37.5, 75, and 150 mg/kg, three times a week for 12 weeks postinfection. After administering the drugs, we monitored the pharmacological performance and anti-parasitic efficacy of ABZ-CS-MPs compared with L-ABZ, and ABZ-T treated mice. ABZ-CS-MPs reduced the weight of tissues containing E. multilocularis metacestodes most effectively compared with the ABZ-T group and untreated controls. Metacestode grown was Highly suppressed during treatment with ABZ-CS-MPs. Significantly higher plasma levels of ABZ metabolites were measured in mice treated with ABZ-CS-MPs or L-ABZ compared with ABZ-T. In particular, enhanced ABZ-sulfoxide concentration profiles were observed in the mice given 150 mg/kg of ABZ-CS-MPs, but not in the mice treated with L-ABZ. Histological examination showed that damages caused disorganization of both the germinal and laminated layers of liver hyatid cysts, demolishing their characteristic structures after treatment with ABZ-CS-MPs or L-ABZ. Over time, ABZ-CS-MPs treatment induced a shift from Th2-dominant to Th1-dominant immune response. CS-MPs As a new carrier exhibited improved absorption and increased bioavailability of ABZ in the treatment of E. multilocularis infections in mice.


Asunto(s)
Albendazol/administración & dosificación , Antihelmínticos/administración & dosificación , Quitosano/administración & dosificación , Portadores de Fármacos/administración & dosificación , Equinococosis Hepática/tratamiento farmacológico , Echinococcus multilocularis/efectos de los fármacos , Microesferas , Administración Oral , Albendazol/farmacocinética , Animales , Antihelmínticos/farmacocinética , Modelos Animales de Enfermedad , Equinococosis , Histocitoquímica , Hígado/parasitología , Hígado/patología , Masculino , Ratones , Plasma/química , Resultado del Tratamiento
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