ALBENDAZOLE-LOADED LIPID NANOCAPSULES IN CYSTIC ECHINOCOCCOSIS: PLASMA/CYST DISPOSITION AND EFFICACY IN INFECTED MICE

PATRICIA EUGENIA PENSEL; GABRIELA ULLIO GAMBOA; JULIA FABBRI; LAURA CEBALLOS; SERGIO F. SANCHEZ BRUNI; LUIS ALVAREZ; DANIEL ALLEMANDI; JEAN PIERRE BENOIT; SANTIAGO DANIEL PALMA; MARÍA CELINA ELISSONDO

Congreso; X Congreso de Protozoología y enfermedades parasitarias; 2014

Cystic echinococcosis (CE) is a zoonotic disease caused by the larval stage of Echinococcus granulosus. The drugs commonly used for anti-hydatid cysts treatment are benzimidazoles. Therapeutic failures following albendazole (ABZ) administration have been primarily linked to the poor drug absorption rate resulting in low drug level in plasma and hydatid cysts. Lipid nanocapsules (LNCs) represent nanocarriers designed to encapsulate lipophilic drugs, such as ABZ. Structurally, the lipophilic drug is solubilised in the lipid core, surrounded by a tensioactive shell. The goals of the current work were: i) to characterize the plasma drug exposure and cyst concentration profiles for ABZ LNCs and ABZ suspension in mice infected with E. granulosus, and ii) to compare ABZ efficacy against secondary CE in mice after the administration of both formulations. Enhanced ABZ sulphoxide (ABZSO) concentration profiles were obtained in plasma and cysts from LNCABZ treated animals. After oral administration of ABZ-LNC, ABZSO exposure was significantly higher in plasma and cyst (area under the concentration-versus-time curve [AUC] plasma = 4.65±0.71 μg. h/mL; cyst = 9.37±1.42 μg. h/g) than that observed after ABZ suspension treatment (AUC plasma= 2.37±0.35 μg. h/mL; cyst = 4.25±0.38 μg. h/g). Additionally, ABZSO concentrations measured in cysts from ABZ-LNC treated mice were 1.5-fold higher than those detected in plasma. This enhanced drug availability correlated with an increased efficacy against secondary CE in mice observed for the ABZ-LNC (0.91±1.16 g), while the suspension formulation (5.38±2.4 g) did not reach differences with the untreated control group (8.98±4.61 g). In conclusion, the improved kinetic behavior of ABZ administered as ABZ-LNC resulted in a higher drug exposure of the hydatid cysts, which enhanced ABZ clinical efficacy on CE developed in mice. This new nanocarrier as drug delivery system for ABZ could be a suitable alternative for treating CE in humans.