Nanostructured lipid carriers containing buparvaquone applied to the canine leishmaniasis treatment: development, physico-chemical evaluation and in vivo leishmanicidal activity

Abstract

Leishmaniases can affect, not only human beings, but also dogs and cats, which are the main reservoirs in urban environments. Canine leishmaniasis, caused by Leishmania infantum, is among the most important vector-borne diseases because of its direct relationship with human cases, according to epidemiological studies. In contrast to the worldwide trend in Brazil, the number of people and animals infected by these parasites has increased. This scenario does not present a prospect of short-term reversal due to the limited treatment availability for humans and animals. Due to the limited number of drugs available, the treatment of pets has been banned for many years in the Brazil, and euthanasia is still the recommended procedure in diagnosed cases. Currently, only one drug, manufactured by Virbac, is available for the pet treatment. Due to its high cost (R$ 6,000.00 per animal per year), treatment is restricted to a small portion of the high-income population. In this way, the impact on Public Health is not significant. Buparvaquone (BPQ), a drug used for veterinary treatment of theileriosis, showed promising in vitro activity against Leishmania parasites. However, due to its low solubility in water and consequent low bioavailability, this drug failed in vivo tests in dogs, intramuscularly. In previous studies, our research group showed increased solubility in aqueous solutions and the in vitro leishmanicidal activity of this drug encapsulated in a nanostructured lipid carrier (NLC). Such innovation made patent application number BR102017021294-7 possible. However, for this innovation to reach the market, different technical-scientific challenges must be overcome. These challenges refer to the development of final product with physicochemical and biological features appropriate to the intended use. Thus, the objectives of the present work are the development, the optimization of physical-chemical features of NLC containing BPQ, the evaluation of its physical-chemical and biological stability and the development of product drying process. In addition, the most suitable administration routes to guarantee the leishmanicidal activity of the developed formulations will be evaluated in hamster. In vivo drug and formulae toxicity, cytokine profile, internalization and cellular localization of the nanoparticles will also be investigated. Our proposal will allow the development of an effective, safe and cost-effective drug compared to the market competitor. (AU)