Development and characterization of a nanomedicine, target driven, to leishmaniasis treatment

Abstract

Leishmaniasis is a group of tropical diseases caused by several species of protozoan parasites belonging to the genus Leishmania. Data from WHO demonstrate that Leishmaniasis affects 12 million people in 88 countries worldwide with approximately 1.3 million new cases annually. The treatment against leishmaniasis is based on pentavalent antimonials, particularly sodium stibogluconate (Pentostam®) and N-methylglucamine antimonate (Glucantime), which are used since 1940. In resistant cases, other drugs such as pentamidine, amphotericin B and paromomycin were reported as a second option, despite its high toxicity. These drugs are parenterally administered in prolonged regimens (at least 20 days), they are toxic and not always effective, leading to an ineffective treatment. In addition, it is reported the resistance of the strains, presence of other diseases and especially low selectivity. The development of a new antiparasite constitutes a scientific and technological challenge, especially because the same need to be able to reach the Leishmania within the phagolysosome of infected macrophages. Infected macrophages may be in the deep dermal layer of the skin in the case of tegumentar leishmaniasis or in liver and spleen cells in visceral leishmaniasis. Given the range of applicability and success that nanostructured systems can bring to various treatments, there are several reports of their implementation, including the leishmaniasis treatment. Different studies have reported the importance of lipid-based carriers such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) due to various advantages that are inherent in nanoparticle systems in general, as drug stability promotion and controlled release, added with peculiar properties as (i) safety, (ii) incorporation of both lipophilic and hydrophilic drugs, (iii) industrial scale-up, and in particular (iv) transport to the lymphatic system after oral administration, promoting drug absorption. Additionally, it is also important to emphasize the possibility of obtaining systems targeted to infected tissue by modulating composition. In this scenario, there is the possibility to employ Lipid Nanoparticulate systems (NLS and NBL) as a reasonable alternative to promote absorption of Amph B administered orally to treat viceral leishmaniasis or topically for the treatment of tegumentar leishmaniais with controlled release. We believe that getting nanodrugs for topical and oral administration is a highly promising proposal and could provide many benefits to patients with leishmaniasis. Thus, both oral and topical administration of Anf B is an attractive idea, since it has the potential to eliminate the acute toxicity associated with administration of the drug intravenously, to reduce and control subacute side effects (renal toxicity), to reduce substantially the costs associated with treatment, improve the quality of life for patients, and allows the therapy to reach developing nations. (AU)