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

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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.

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Acknowledgments

The authors would like to thank Dr. Daniel Brusa (CEMETRO, Universidad Tecnológica Nacional, Facultad Regional Córdoba, Córdoba, Argentina) for assistance with atomic force imaging. The authors are also grateful to the technical staff Nolwenn Lautram and Béjaud Jérôme (INSERM U1066, Micro et Nanomédecines biomimétiques, IBS-CHU Angers, France) for their help in skillful technical support. Ms. Gabriela Ullio Gamboa thanks the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) for a research fellowship. This work was supported by the grants SECyT-UNC [Res. 162/12] and CONICET [PID N° 11220090100673].

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Authors and Affiliations

  1. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica, UNITEFA-CONICET, Ciudad Universitaria, 5000, HUA, Córdoba, Argentina

    G. V. Ullio Gamboa, S. D. Palma & D. A. Allemandi

  2. LUNAM Université, Université d’Angers, INSERM U1066, IBS-CHU, Angers, 4 rue Larrey, 49933, Angers, France

    C. Passirani & J. P. Benoit

  3. Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil, CIVETAN (CONICET), Fac.Cs. Veterinarias, UNCPBA, Tandil, Argentina

    A. Lifschitz, M. Ballent & C. Lanusse

  4. Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000, HUA, Córdoba, Argentina

    G. V. Ullio Gamboa, S. D. Palma & D. A. Allemandi

Authors
  1. G. V. Ullio Gamboa
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  2. S. D. Palma
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  3. A. Lifschitz
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  4. M. Ballent
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  5. C. Lanusse
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  6. C. Passirani
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  7. J. P. Benoit
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  8. D. A. Allemandi
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Correspondence to D. A. Allemandi.

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Gamboa, G.V.U., Palma, S.D., Lifschitz, A. et al. Ivermectin-loaded lipid nanocapsules: toward the development of a new antiparasitic delivery system for veterinary applications. Parasitol Res 115, 1945–1953 (2016). https://doi.org/10.1007/s00436-016-4937-1

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  • DOI: https://doi.org/10.1007/s00436-016-4937-1

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