Cystic echinococcosis therapy: Albendazole-loaded lipid nanocapsules enhance the oral bioavailability and efficacy in experimentally infected mice

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

ACTA TROPICA

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2015 vol. 152 p. 184 - 195

0001-706X

Therapeutic failures attributed to medical management of cystic echinococcosis (CE) with albendazole(ABZ) have been primarily linked to the poor drug absorption rate resulting in low drug level in plasma andhydatid cysts. Lipid nanocapsules (LNCs) represent nanocarriers designed to encapsulate lipophilic drugs,such as ABZ. The goals of the current work were: (i) to characterize the plasma and cyst drug exposure afterthe administration of ABZ as ABZ-LNCs or ABZ suspension (ABZ-SUSP) in mice infected with Echinococcusgranulosus, and ii) to compare the clinical efficacies of both ABZ formulations. Enhanced ABZ sulphox-ide (ABZ-SO) concentration profiles were obtained in plasma and cysts from ABZ-LNC treated animals.ABZSO exposure (AUC0?LOQ) was significantly higher in plasma and cyst after the ABZ-LNC treatments,both orally and subcutaneously, compared to that observed after oral administration of ABZ-SUSP. Addi-tionally, ABZSO concentrations measured in cysts from ABZ-LNC treated mice were 1.7-fold higher thanthose detected in plasma. This enhanced drug availability correlated with an increased efficacy againstsecondary CE in mice observed for the ABZ-LNCs, while ABZ-SUSP did not reach differences with theuntreated control group. This new pharmacotechnically-based strategy could be a potential alternativeto improve the treatment of human CE.