Development of an injectable formulation of albendazole and in vivo evaluation of its efficacy against Echinococcus multilocularis metacestode.
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 microgram 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.
Rodrigues
J M
JM
Laboratoire de Pharmacie Galénique et Biopharmacie, URA CNRS 1218, Université Paris XI, Chatenay-Malabry, France.
Bories
C
C
Emery
I
I
Fessi
H
H
Devissaguet
J P
JP
Liance
M
M
D015766:Albendazole / Q000008:administration & dosage*; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage*; D003102:Colloids; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical; D004444:Echinococcosis, Hepatic / Q000188:drug therapy* / Q000469:parasitology; D004446:Echinococcus / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D011091:Polyesters
D000871:Anthelmintics; D003102:Colloids; D004337:Drug Carriers; D011091:Polyesters; C033616:poly(lactide); D015766:Albendazole