Ivermectin-loaded lipid nanocapsules: toward the development of a new antiparasitic delivery system for veterinary applications

GABRIELA ULLIO GAMBOA,; PALMA S. D; LIFSCHITZ, A.; BALLENT, LAURA; LANUSSE , C; PASSIRANI C. ,; BENOIT J; ALLEMANDI D,

PARASITOLOGY RESEARCH

SPRINGER

Lugar: Berlin; Año: 2016 vol. 115 p. 1945 - 1953

0932-0113

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.