Desenvolvimento, caracterização e avaliação da imunomodulação de nanoemulsão óleo em água contendo carvacrol

Abstract

Carvacrol (CV) is an essential oil that has several therapeutic properties, including immunomodulatory activity. However, this active has some physicochemical properties that hinder its use in the biological therapeutic environment, such as high lipophilicity, sensitivity to degradation when in contact with light, and easy oxidation. Furthermore, the immunomodulatory effect has not been studied in nanoemulsion systems, which The nanoemulsification process can help to limit the VC and improve its therapeutic immunomodulatory activity. Thus, the aim of this study was to develop and characterize a nanoemulsified system containing CV and evaluate its immunomodulatory action. Carvacrol nanoemulsion (CVNE) and white nanoemulsion (BNE) were produced by the sonication technique. The physicochemical characterization of nanoemulsions was carried out by evaluating the zeta potential, polydispersion index and average droplet size over 90 days by the dynamic light scattering (DLS) technique. Cytotoxic activity and cytokine quantification (IL-1β; IL-2; IL-6; IL-10; IL-17; IFN-γ; and TNF-α) were evaluated in peripheral blood mononuclear cell culture supernatants (PBMCs) using the MTT assay [3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium], at concentrations of 50 μM, 100 μM and 200 μM CV The nanoemulsion of CV (CVNE) is composed of 5% w/w oil phase, 2% w/w surfactants and 93% w/w water. The white nanoemulsion CVNE (BNE) has the same composition without carvacrol, and was obtained an encapsulation efficiency of 83.97% ± 1.02 from the ultraviolet-visible spectrophotometer. CVNE achieved encapsulation efficiency of 83% ± 1.02 , droplet size of 165.70 ± 0.46nm, PDI of 0.14 ± 0.03, zeta potential of -10.25 ± 0.52 mV and good stability for 90 days. CVNE did not show relevant cytotoxicity activity up to 200 μM in peripheral blood mononuclear cells at the concentrations studied. Immunomodulation studies demonstrated that carvacrol nanoemulsification CVNE improved its biological response, reducing the levels of pro-inflammatory cytokines IL-2, IL-17 and IFN-γ to 50 μM. In conclusion, a carvacrol nanoemulsion was produced showing an improvement in the immunomodulatory activity of CV in PBMCs. However, for a better understanding of the mechanism of action it is necessary to perform in vivo tests, and oral absorption tests.