title: Cystic echinococcosis therapy: Albendazole-loaded lipid nanocapsules enhance the oral bioavailability and efficacy in experimentally infected mice.
abstract: 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 and hydatid 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 after the administration of ABZ as ABZ-LNCs or ABZ suspension (ABZ-SUSP) in mice infected with Echinococcus granulosus, and ii) to compare the clinical efficacies of both ABZ formulations. Enhanced ABZ sulphoxide (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. Additionally, ABZSO concentrations measured in cysts from ABZ-LNC treated mice were 1.7-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-LNCs, while ABZ-SUSP did not reach differences with the untreated control group. This new pharmacotechnically-based strategy could be a potential alternative to improve the treatment of human CE.
authors.affiliation: Laboratorio de Zoonosis Parasitaria, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Funes 3250, 7600 Mar del Plata, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Pensel
authors.affiliation: Unidad de Investigación y Desarrollo en Tecnología Farmacéutica, UNITEFA-CONICET, Ciudad Universitaria, 5000 HUA, Córdoba, Argentina; Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 HUA, Córdoba, Argentina.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Ullio Gamboa
authors.affiliation: Laboratorio de Zoonosis Parasitaria, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Funes 3250, 7600 Mar del Plata, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Julia
authors.initials: J
authors.lastname: Fabbri
authors.affiliation: Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN), Facultad de Ciencias Veterinarias, UNCPBA-Tandil, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Ceballos
authors.affiliation: Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN), Facultad de Ciencias Veterinarias, UNCPBA-Tandil, Argentina.
authors.forename: Sergio
authors.initials: S
authors.lastname: Sanchez Bruni
authors.affiliation: Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN), Facultad de Ciencias Veterinarias, UNCPBA-Tandil, Argentina.
authors.forename: Luis I
authors.initials: LI
authors.lastname: Alvarez
authors.affiliation: Unidad de Investigación y Desarrollo en Tecnología Farmacéutica, UNITEFA-CONICET, Ciudad Universitaria, 5000 HUA, Córdoba, Argentina; Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 HUA, Córdoba, Argentina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Allemandi
authors.affiliation: LUNAM Université, Université d'Angers, INSERM U1066, IBS-CHU Angers, 4 rue Larrey, 49933 Angers, France.
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Benoit
authors.affiliation: Unidad de Investigación y Desarrollo en Tecnología Farmacéutica, UNITEFA-CONICET, Ciudad Universitaria, 5000 HUA, Córdoba, Argentina; Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 HUA, Córdoba, Argentina.
authors.forename: Santiago D
authors.initials: SD
authors.lastname: Palma
authors.affiliation: Laboratorio de Zoonosis Parasitaria, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Funes 3250, 7600 Mar del Plata, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Electronic address: c.elissondo@gmail.com.
authors.forename: María C
authors.initials: MC
authors.lastname: Elissondo
mesh_terms: D000284:Administration, Oral; D015766:Albendazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D004443:Echinococcosis / Q000188:drug therapy*; D048209:Echinococcus granulosus; D005260:Female; D008055:Lipids / Q000008:administration & dosage; D051379:Mice; D053769:Nanocapsules
chemical_list: D000871:Anthelmintics; D008055:Lipids; D053769:Nanocapsules; D015766:Albendazole
keywords: Albendazole; Cystic echinococcosis; Echinococcus granulosus; Lipid nanocapsules