Development of Environmentally Responsive Self-Emulsifying System Containing Copaiba Oil-Resin for Leishmaniasis Oral Treatment.

Abstract

Leishmaniasis is a disease caused by protozoa species of the Leishmania genus, and the current treatments face several difficulties and obstacles. Most anti-leishmanial drugs are administered intravenously, showing many side effects and drug resistance. The discovery of new anti-leishmanial compounds and the development of new pharmaceutical systems for more efficient and safer treatments are necessary. Copaiba oil-resin (CO) has been shown to be a promising natural compound against leishmaniasis. However, CO displays poor aqueous solubility and bioavailability. Self-emulsifying drug delivery systems (SEDDS) can provide platforms for release of hydrophobic compounds in the gastrointestinal tract, improving their aqueous solubilization, absorption and bioavailability. Therefore, the present work aimed to develop SEDDS containing CO and Soluplus® surfactant for the oral treatment of leishmaniasis. The design of the systems was accomplished using ternary phase diagrams. Emulsification and dispersion time tests were used to investigate the emulsification process in gastric and intestinal environments. The formulations were nanostructured and improved the CO solubilization. Their in vitro antiproliferative activity against promastigote forms of L. amazonensis and L. infantum, and low in vitro cytotoxicity against macrophages were also observed. More studies are necessary to determine effectiveness of SOL in these systems, which can be candidates for further pharmacokinetics and in vivo investigations.