RESUMO
Neutrophils play an important role in the pathophysiology of inflammatory processes, where their concentration and activity are usually extremely high, due to a variety of soluble factors, namely cytokines and chemokines. Cytokines and chemokines are responsible for the delay of the neutrophils' constitutive apoptotic pathway, contributing for their accumulation at the inflammatory site, potentiating the tissue damage by the continuous production of reactive oxygen species and granule enzymes. Thus, the modulation of neutrophils' apoptosis and the production of cytokines and chemokines are seen as new therapeutic targets.[1] Flavonoids may be considered promising molecules in the resolution of the inflammatory process, due to their potential to interfere with pro-inflammatory signaling pathways. In this study, a series of flavonoids were tested for their capacity to interfere in human neutrophils apoptosis, assessed by flow cytometry after simultaneous staining with Annexin-V labeled with fluorescein and propidium iodide.[2] Their capacity to modulate the production of cytokines and chemokines were also evaluated, in human whole blood, using a commercial ELISA kit.[3] The studied flavonoids showed promising features for simultaneously induce apoptosis and inhibit the cytokines / chemokine's production. Overall, this work reveals promising flavonoids for the modulation of the inflammatory process.
RESUMO
INTRODUCTION: Resveratrol is a polyphenol found in grapes and red wines. Interest in this polyphenol has increased due to its pharmacological cardio- and neuroprotective, chemopreventive, and antiaging effects, among others. Nevertheless, its pharmacokinetic properties are less favorable, since the compound has poor bioavailability, low water solubility, and is chemically unstable. To overcome these problems, we developed two novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance resveratrol's oral bioavailability for further use in medicines, supplements, and nutraceuticals. METHODS AND MATERIALS: Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with resveratrol were successfully produced by a modified hot homogenization technique. These were completely characterized to evaluate the quality of the developed resveratrol-loaded nanoparticles. RESULTS: Cryo-scanning electron microscopy morphology studies showed spherical and uniform nanoparticles with a smooth surface. An average resveratrol entrapment efficiency of ~70% was obtained for both SLNs and NLCs. Dynamic light scattering measurements gave a Z-average of 150-250 nm, polydispersity index of ~0.2, and a highly negative zeta potential of around -30 mV with no statistically significant differences in the presence of resveratrol. These characteristics remained unchanged for at least 2 months, suggesting good stability. Differential scanning calorimetry studies confirmed the solid state of the SLNs and NLCs at both room and body temperatures. The NLCs had a less ordered crystalline structure conferred by the inclusion of the liquid lipid, since they had lower values for phase transition temperature, melting enthalpy, and the recrystallization index. The presence of resveratrol induced a disorder in the crystal structure of the nanoparticles, suggesting a favoring of its entrapment. The in vitro release studies on conditions of storage showed a negligible resveratrol release over several hours for both nanosystems and the in vitro simulation of gastrointestinal transit showed that the resveratrol remained mostly associated with the lipid nanoparticles after their incubation in digestive fluids. CONCLUSION: Both nanodelivery systems can be considered suitable carriers for oral administration, conferring protection to the incorporated resveratrol and allowing a controlled release after uptake.
