Development and characterization of target-driven nanotechnology based drug for Leishmaniasis treatment

Abstract

Leishmaniasis is a group of tropical diseases caused by several species of protozoan parasites belonging to the genus Leishmania. WHO data show that Leishmaniasis reaches 12 million people in 88 countries worldwide with about 1.3 million new cases annually. Treatment for leishmaniasis is based on pentavalent antimonials, mainly sodium stibogluconate (Pentostam®) and N-methylglucamine antimoniate (Glucantime®), which have been used since 1940. In resistant cases, other drugs such as pentamidine, amphotericin B and paromomycin were reported as a second option, despite their high toxicity. These drugs are administered parenterally in prolonged dosing schedules (at least 20 days), are toxic and not always effective, leading to ineffective treatment. In addition, the resistance of the strains, the presence of other associated diseases and mainly the low selectivity are reported. The development of a new antiparasitic constitutes a scientific and technological challenge, especially because it must be able to reach Leishmania within the phagocytosome of infected macrophages that may now be in the dermal layer of the deep skin in the case of American cutaneous leishmaniasis in liver cells, spleen in visceral leishmaniasis (VL). In view of the range of applicability and success that nanostructured systems can bring to various treatments, there are several reports of its application including for leishmaniasis. Different studies have reported the importance of lipid-based carriers such as solid lipid nanoparticles (NLS) and nanostructured lipid carriers (CLN) because of the various advantages inherent in nanoparticulate systems in general, such as promoting drug stability, controlled release, (ii) incorporation of both lipophilic and hydrophilic drugs, (iii) industrial staging, and especially (iv) transportation through the lymphatic system after oral administration, promoting drug absorption. Additionally, it is still important to emphasize the possibility of obtaining systems directed to the infected tissue through the modulation of its composition. In this scenario, the possibility of using Nanoparticulate Lipid Systems (NLS and CLN) as a plausible alternative to promote the absorption of Anf B orally administered for treatment of LV or topical route for treatment of American tegumentary leishmaniasis (LTA) with release. We believe that obtaining nanomedications with topical and oral application are characterized as a highly promising proposal that can provide many benefits for patients with leishmaniasis. Thus, oral and / or topical administration of Anf B is an attractive idea as it has the potential to eliminate the acute toxicity associated with intravenous drug administration, reduce and control subacute side effects (renal toxicity), substantially reduce costs associated with treatment, improve quality of life for patients, and enable therapy to reach developing nations. (AU)