Nanoemulsões biocompatíveis para o tratamento da doença de Chagas

Abstract

Neglected diseases, including Chagas disease, represent a global health problem due to the industry's lack of interest in research for new drugs. Benznidazole (BNZ), a drug available in Brazil for the treatment of Chagas disease, and distributed by the Health Ministery, presents some limitations regarding its use, especially in the chronic phase of the disease. Pharmaceutical technology provides the development of systems that increase drug solubility or increase its concentration in infected cells / tissues which directly reflects the increased bioavailability and therapeutic efficacy of BNZ. Thus, liquid systems such as lipid colloidal systems (LCS), such as emulsions, microemulsions, nanoemulsions are an interesting alternative for increasing oral and parenteral bioavailability of BNZ. This work aims to develop biocompatible nanoemulsions containing medium chain triglycerides (Miglyol®812) stabilized by a suitable mixture of surfactants (soybean phosphatidylcholine and sodium oleate), and to evaluate the trypanocidal effect. The ideal conditions for obtaining the systems of interest were evaluated by the study of phase inversion temperature (PIT) and the addition of a new component. Nanoemulsions were formed with addition of 2-methylpyrrolidone (NMP) with uniform droplet size and less than 162.66 nm. The systems remained stable for up to 60 days when stored at 25 ° C. The rheological properties showed a behavior dependent on the amount of co-solvent added to the system. The polarized light microscopy and low angle X-ray scattering images confirmed the formation of isotropic systems when the cosolvent is in a concentration greater than 5%. The release of BNZ in systems containing sialic acid at different concentrations was up to 3 (three) times faster than systems without the substance. The systems showed biocompatibility in different cell lines (Vero, SiHa and LLCMK2). Nanoemulsions were able to transport BNZ in biocompatible systems with excellent trypanocidal activity, thus representing a promising future in the treatment of Chagas' disease, considering that to date there are no liquid dosage forms of administration, which makes it impossible to adjust the dose and decrease of side effects.