Desenvolvimento de sistemas nanoestruturados contendo óleo de candeia para tratamento tópico da leishmaniose cutânea

Abstract

Leishmaniasis is a neglected, re-emergence disease that presents serious problems in the world, causing morbidity and skin damage that persists for years or even years. The treatment of leishmaniasis involves serious adverse effects and resistance to the main drugs used. Based on the clinical scenario, natural products isolated to the new antileishmania development agents by the diversity of their economical products and less, new targets. The essential oil of Eremanthus erythropappus, popularly known as oil of candeia (OEC), is rich in alpha-bisabolol, which, in previous studies, showed antileishmanial action in vitro. Thus, the objective of this work is to develop and characterize microemulsions and liquid crystalline systems containing OEC for the treatment of leishmaniasis topic. Initially, the OEC was developed for coupling Gas Chromatography Detector by Mass Spectrometry. Then, the nanostructured systems were through Diagrams obtained from Pseudoternary Phases, using OEC as the oil phase, eumulgin®CO 40, as a surfactant, olivem®300 or polymol®HE, as a co-surfactant, in a 1:1 ratio, and distilled water as the aqueous phase. The transparent systems obtained were characterized by polarized light microscopy and rheological behavior. From these results, a transparent liquid system (SLT) with 5% of oil phase and with a lower surfactant was selected from each concentration diagram, and a transparent viscous system (SVT) with 5% of oil phase and with a concentration of 55% surfactant. The SLTs were also obtained in terms of droplet size and polydispersity index (IPD). Additionally, the pH of the selected formulations was determined, the interaction of the formulations with the stratum corneum (EC) was evaluated using the FTIR technique, and, finally, the cytotoxicity and antileishmanial activity of the formulations and isolated OEC were investigated. For this, inhibitory concentrations (IC50) against promastigote forms of L. amazonensis, L. brasiliensis and L. major and intracellular amastigotes of L. amazonensis were determined. As a result, it was observed that all SLTs showed isotropy and newtonian behavior, characteristic of ME. The SVT, on the other hand, showed a non-newtonian behavior, characteristic of CLs. Regarding pH, the selected SVT presented pH 6.1, and the SLT presented pH between 6.5 and 6.9, compatible with physiological pH, and droplet size and IPD below 25 nm and 0.3, respectively. FTIR analysis showed that the formulations can interact with the EC barrier promoting alpha-bisabolol skin penetration. The selected MEs showed higher activity (IC50) against promastigotes, when compared to the OEC. Regarding the antileishmanial activity against intracellular amastigotes of L. amazonensis, the IC50 results of the formulations F5C25, F5CO25 and F5CP25 (IC50 3.37, 5.25 and 3.98µg. mL-1 respectively), were at least 33 times higher efficient when compared to the OEC (IC50 172.8 µg. mL-1 ). The Selectivity Index (IS) was calculated and the results were IS >7, and the ME F5C25 presented IS=14.9 the best result among the developed formulations. The present study showed that the MEs, containing OEC, showed in vitro activity against L. amazonensis, which provides basic foundations for further in vivo studies.