Evaluation of a potential alternative to the treatment of human neurocysticercosis: albendazole-loaded lipid nanocapsules enhance the bioavailability of albendazole in the brain of healthy mice.

FABBRI JULIA; ESPINOZA JUAN PABLO; PENSEL, PATRICIA EUGENIA; ALBANI CLARA MARÍA; MEDICI SANDRA; ULLIO GAMBOA G.; BENOIT J. P.; ELISSONDO MARIA CELINA

Mar del Plata

Congreso; Reunión Conjunta SAIC-SAFE- SAB-SAP-NANOMED-ar- AACYTAL -2019; 2019

Neurocysticercosis (NCC) is a zoonotic disease caused by encystment of Taenia solium larvae in the central nervous system. Pharmacological treatment is performed with albendazole (ABZ). However, the slow rate of dissolution of ABZ produces a poor and erratic absorption of the drug at the gastrointestinal level. This produces wide variability in plasma and cerebrospinal fluid concentrations of the drug among patients, with variations in treatment efficacy. Lipid nanocapsules (LNCs) are drug carrier nanosystems designed to solubilize lipophilic drugs. The aim of the present work was to characterize and compare the brain pharmacokinetic behavior of a suspension of ABZ (ABZ-SUSP) or ABZ-LNCs in healthy mice. Animal procedures and management protocols were approved by the Institutional Animal Care and Use Committee (RD 148/15) of the FCEyN, UNMdP. CF-1 mice were separated into two groups (n = 44): ABZ-SUSP and ABZ-LNCs. In both cases, a single dose of 5 mg/kg of ABZ was administered orally. The brains were recovered at different post-treatment times until 16 h. The samples were analyzed by high performance liquid chromatography to quantify ABZ and its metabolites. Enhanced ABZ sulfoxide concentration profile was obtained in brains from ABZ-LNCs treated animals. Higher metabolite brain exposure was obtained after administration of ABZ-LNCs formulation to mice (area under the concentration versus time curve (AUC) = 0.82 ± 0.17 mg.h/kg and peak concentration (Cmax) = 0.14 ± 0.03 mg/kg) compared to the ABZ-SUSP (AUC = 0.29 ± 0.05 mg.h/kg and Cmax = 0.072 ± 0.01 mg/kg) (P < 0.05). The improvement of the brain availability of ABZ observed after the administration of ABZ-LNCs to healthy mice worth to be evaluated on an animal model of NCC. This new nanocarrier as drug delivery system for ABZ could be a suitable alternative for treating NCC in humans.