Institution: | a Laboratoire de Pharmacie Galénique et Biopharmacie, URA CNRS 1218, Université Paris XI, 92296, Chatenay-Malabry, France b Laboratoire de Parasitologie, Université Paris XI, 92296, Chatenay-Malabry, France c Laboratoire de Parasitologie, Faculté de Médecine, 6 Rue du Général Sarrail, 94010, Créteil, France d Laboratoire de Galénique, Faculté de Pharmacie, 8 Avenue Rockefeller, 69373, Lyon Cedex 08, France |
Abstract: | The loading of poly (D,L-lactide) nanoparticles with ABZ has led us to evaluate the potential of this new colloidal drug delivery system against E. multilocularis, using a murine model of hepatic alveolar echinococcosis. ABZ-loaded nanoparticles had a monodisperse size distribution between 100 and 150 nm. The efficiency of drug loading to nanoparticles was over 97%. In vitro, at an ABZ concentration of 1.0 μg ml−1, the formulation had no toxicity for peritoneal macrophages harvested from uninfected mice, In vivo, the ABZ-loaded nanoparticles exhibited no signs of toxicity at any of the doses tested. Intravenous injections of 6 mg kg−1 of bound ABZ to infected mice had an equivalent antiparasitic effect on the metacestode growth to that of a treatment with 1500 mg kg−1 of orally administered free ABZ. The parasite hepatic superficial size as well as the peritoneal metastatic burden was significantly reduced by these 2 courses of treatment, as compared to those of untreated mice. Our results should encourage further study in order to explain the absence of dose-dependent efficacy of ABZ-loaded nanoparticles demonstrated in the present study. |