Complexo anfífílico de antimônio: atividade leishmanicida in vitro e eficácia de uma formulação tópica em modelo murino de leishmaniose cutânea.

Abstract

Leishmaniasis is considered a major public health problem in 88 countries worldwide. It is considered a neglect disease by The World Health Organization, thus reinforcing the need of new effective and less toxic compounds. The available drugs require long-term treatment and cause several side effects. In addition to the development of new drugs, another strategy is to enhance the leishmanicidal activity of available drugs and decrease its toxicity. LA8 is an amphiphilic alquilmetilglucamida that binds to pentavalent antimony and is a potentially effective molecule against leishmaniasis. The aim of this study was to evaluate its in vitro and in vivo efficacy against Leishmania amazonensis infected BALB/c mice with by a topical formulation. Also, in vitro assays using mice peritoneal macrophages showed that the complex LA8-Sb was about 100 times more toxic (CC50 = 0.26mM Sb) than Glucantime (CC50 = 26.31mM Sb) and 6 times more toxic than LA8 and its ligand alone (CC50 = 4.89mM LA8). There is no anti-amastigote activity after 72 hours of exposure, in concentrations below the cytotoxic concentration (CC 50), when incubated in infected with L. amazonensis murine peritoneal macrophages. BALB/c mice were inoculated at the tail base with L. amazonensis and treated twice a day for 3 weeks with a topical formulation containing LA8-Sb. This assay resulted in stabilization of the lesion size and a decrease in parasite burden. The percutaneous permeation of the antimony present in the complex was evaluated by the Franz diffusion cell model. The antimony permeations were about 0.008% and 4.27% in the intact and stripped skin, respectively. The present study shows that the topical formulation, despite the in vitro results may present an anti-leishmania activity in vivo. Further studies are needed to elucidate the potential effectiveness of the LA8-Sb.