title: Ivermectin-loaded lipid nanocapsules: toward the development of a new antiparasitic delivery system for veterinary applications.
abstract: Ivermectin (IVM) is probably one of the most widely used antiparasitic drugs worldwide, and its efficacy is well established. However, slight differences in formulation may change the plasma kinetics, the biodistribution, and in consequence, the efficacy of this compound. The present study focuses on the development of a novel nanocarrier for the delivery of lipophilic drugs such as IVM and its potential application in antiparasitic control. Lipid nanocapsules (LNC) were prepared by a new phase inversion procedure and characterized in terms of size, surface potential, encapsulation efficiency, and physical stability. A complement activation assay (CH50) and uptake experiments by THP-1 macrophage cells were used to assess the stealth properties of this nanocarrier in vitro. Finally, a pharmacokinetics and biodistribution study was carried out as a proof of concept after subcutaneous (SC) injection in a rat model. The final IVM-LNC suspension displayed a narrow size distribution and an encapsulation rate higher than 90 % constant over the evaluated time (60 days). Through flow cytometry and blood permanence measurements, it was possible to confirm the ability of these particles to avoid the macrophage uptake. Moreover, the systemic disposition of IVM in the LNC administered by the SC route was higher (p < 0.05) (1367 ng h/ml) compared to treatment with a commercial formulation (CF) (1193 ng.h/ml), but no significant differences in the biodistribution pattern were found. In conclusion, this new carrier seems to be a promising therapeutic approach in antiparasitic control and to delay the appearance of resistance.
authors: 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: G V Ullio
authors: GV
authors: Gamboa
authors: 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: S D
authors: SD
authors: Palma
authors: Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil, CIVETAN (CONICET), Fac.Cs. Veterinarias, UNCPBA, Tandil, Argentina.
authors: A
authors: A
authors: Lifschitz
authors: Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil, CIVETAN (CONICET), Fac.Cs. Veterinarias, UNCPBA, Tandil, Argentina.
authors: M
authors: M
authors: Ballent
authors: Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil, CIVETAN (CONICET), Fac.Cs. Veterinarias, UNCPBA, Tandil, Argentina.
authors: C
authors: C
authors: Lanusse
authors: LUNAM Université, Université d'Angers, INSERM U1066, IBS-CHU, Angers, 4 rue Larrey, 49933, Angers, France.
authors: C
authors: C
authors: Passirani
authors: LUNAM Université, Université d'Angers, INSERM U1066, IBS-CHU, Angers, 4 rue Larrey, 49933, Angers, France.
authors: J P
authors: JP
authors: Benoit
authors: Unidad de Investigación y Desarrollo en Tecnología Farmacéutica, UNITEFA-CONICET, Ciudad Universitaria, 5000, HUA, Córdoba, Argentina. dalemand@gmail.com.|Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000, HUA, Córdoba, Argentina. dalemand@gmail.com.
authors: D A
authors: DA
authors: Allemandi
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000627:therapeutic use*; D004333:Drug Administration Routes; D004337:Drug Carriers; D007279:Injections, Subcutaneous; D007559:Ivermectin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008055:Lipids / Q000737:chemistry*; D008264:Macrophages / Q000378:metabolism; D053769:Nanocapsules / Q000737:chemistry*; D051381:Rats; D014018:Tissue Distribution
chemical_list: D000977:Antiparasitic Agents; D004337:Drug Carriers; D008055:Lipids; D053769:Nanocapsules; D007559:Ivermectin
keywords: Drug delivery systems; Ivermectin; Lipid nanocapsules; Pharmacokinetic; Tissue distribution