In vivo efficacy of albendazole formulated as solid dispersions against Echinococcus multilocularis

JULIA FABRI, ; PATRICIA PENSEL,; CLARA MARIA ABANI; ANALIA SIMONAZZI,; SANTIAGO PALMA; CELINA ELISSONDO.

Lima

Congreso; XXVIII World Congress on Echinococcosis; 2019

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The treatment of human alveolar echinococcosis consists of surgery and/orchemotherapy with benzimidazoles-methylcarbamates, mainly albendazole (ABZ). Thisdrug has limited efficacy due to its poor and erratic bioavailability, attributed to its lowdissolution rate. Solid dispersions (DSs) are considered a successful strategy to improvethe dissolution profile and consequently the absorption of poorly soluble drugs such asABZ. DSs are defined as the dispersion of one or more drugs in an inert carrier or matrixin the solid state. Recently, ABZ DSs have been developed using Poloxamer 407 (P407)as a carrier. This formulation significantly increased the solubility and dissolution rate ofABZ. The aim of the present work was to evaluate the clinical efficacy of ABZ:P407 DSsin mice infected with Echinococcus multilocularis. Fifty CF-1 mice were infectedintraperitoneally with metacestodes of E. multilocularis. Six weeks post-infection, themice were divided into 5 groups: 1- Water control; 2- P407 control; 3- ABZcarboxymethylcellulose suspension; 4- Physical mixture (ABZ+P407) and 5- ABZ:P407DSs. The treatments were performed orally, every 24 hours for 30 days. In all cases, theABZ dose was 25 mg/kg. At the end of the treatment (approximately 10 weeks postinfection), mice were euthanized and the metacestodes were recovered. The efficacy oftreatments was evaluated by comparing the weight of the cysts and by the ultrastructural alterations studied by scanning electron microscopy. No significant differences wereobserved between the weight of the cysts recovered from the control groups (P>0.05).All the treatments decreased the development of the cysts. However, only the micetreated with the ABZ:P407 DSs showed a significant decrease in the weight of the cysts(P