High efficacy of albendazole-PEG 6000 in the treatment of Toxocara canis larva migrans infection

Abstract

Objectives: In vitro and in vivo experiments were used to determine whether albendazole-PEG 6000 solid dispersions would be effective in the treatment of Toxocara canis larva migrans. Methods: Albendazole-PEG 6000 (1:1, 1:5 and 1:9 ratios) solid dispersions were prepared by the solvent evaporation method. The morphology of the particles was evaluated by scanning electron microsocopy (SEM), and in vitro dissolution assays were also carried out. Mice were infected with T. canis and then treated orally with albendazole-PEG 6000 systems or albendazole suspended in water. The anthelmintic effect was examined at 28 days post-infection (p.i.). The number of larvae recovered from mice treated with albendazole alone and those treated with albendazole-PEG 6000 were compared with the numbers from the placebo group. Results: Dissolution of albendazole from solid dispersions was markedly enhanced by increasing the polymer concentration. At a 1:9 drug:polymer ratio, >90% of the albendazole was dissolved in 10 min. SEM showed microparticles to be of small spherical shape compared with the pure components. In vivo evaluation of larva migration showed that both albendazole-PEG 6000 solutions exhibited a greater anthelmintic effect in the brain (0 larvae/mouse). In addition it was also found that liver and lung showed a significant decrease in the number of larvae. Evaluation of vehicle toxicity (PEG 6000 in water) showed a mice survival rate of 100% at the assayed concentrations. Conclusions: These data suggest that albendazole-PEG 6000 solid dispersions markedly increased the effectiveness of albendazole against the migratory activity of larvae. Particularly, these polymeric solutions were able to totally prevent migration of larvae to the mouse brain. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.