Efficacy of Albendazole-Chitosan Microsphere-based Treatment for Alveolar Echinococcosis in Mice

• Published in: PLoS neglected tropical diseases Vol. 9; no. 9; p. e0003950
• Main Authors: Abulaihaiti, Maitiseyiti, Wu, Xiang-Wei, Qiao, Lei, Lv, Hai-Long, Zhang, Hong-Wei, Aduwayi, Nasrul, Wang, Yan-Jie, Wang, Xin-Chun, Peng, Xin-Yu
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.09.2015; Public Library of Science (PLoS)
• Subjects: Administration, Oral; Albendazole; Albendazole - administration & dosage; Albendazole - pharmacokinetics; Animals; Anthelmintics - administration & dosage; Anthelmintics - pharmacokinetics; Bioavailability; Chitosan - administration & dosage; Cytokines; Disease Models, Animal; Dosage and administration; Drug Carriers - administration & dosage; Drug delivery systems; Drug dosages; Drug therapy; Drugs; Echinococcosis; Echinococcosis, Hepatic - drug therapy; Echinococcus multilocularis - drug effects; Experiments; Histocytochemistry; Infections; Liver - parasitology; Liver - pathology; Male; Medical research; Mice; Microspheres; Observations; Parasites; Plasma - chemistry; Rodents; Testing; Treatment Outcome; Vehicles
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0003950

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.