Desenvolvimento de micropartículas de fluoxetina com galactomanana e a avaliação da sua atividade in vitro frente as cepas de Staphylococcus aureus resistente a meticilina

Abstract

The emergence of multi-resistant bacteria (MDR) is a global problem, as it reduces the effectiveness of traditional antibiotics and reduces the therapeutic arsenal to treat bacterial infections. This has led to an increase in research on how to overcome this resistance to antibiotics. One strategy is to reposition (or reuse) existing drugs not previously used to fight microorganisms, instead of developing new drugs. Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRIs) and is considered one of the first highly selective antidepressants of the neurotransmitter monoamine serotonin (5-HT). The aim of this study is to prepare and physically characterize fluoxetine microparticles with galactomannan, to evaluate their efficacy against methicillin-resistant Staphylococcus aureus strains and to evaluate the potential for genotoxicity and mutagenicity of fluoxetine and microparticles obtained through the chromosomal and aberration test Salmonella / microsomal mutagenicity assay. The microparticles were analyzed by differential scanning calorimetry (DSC), infrared (IR) analysis and X-ray diffraction (XRD). In addition, the encapsulation efficiency percentage (EE%) and the drug release kinetics were determined in vitro, together with the determination of the minimum inhibitory concentration (MIC) and evaluation of the action against biofilms. Physical tests were performed to characterize galactomannan (GAL), FLX, oxacillin (OXA) and galactomannan / fluoxetine (GFM) microparticles. The EE% value was 98% and, in relation to the release, the tests with the microparticles released about 60% of the drug in 200 minutes. The results of isolated MIC for FLX (255 µg / mL) and OXA MIC (1.97-15.62 µg / mL) showed that the strains were resistant. In addition, in biofilms, microparticles showed a statistically significant improvement for all concentrations used. The study revealed that fluoxetine encapsulated in microparticles has the potential to act as an effective antimicrobial agent and that fluoxetine can cause chromosomal changes and mutagenic rates at higher concentrations, while fluoxetine encapsulated in galactomannan did not cause these changes.