Glycerol monostearate solid lipid nanoparticles (SLN) were produced by hot high-pressure homogenization technique to load alpha-pinene, citral, geraniol or limonene. SLN were composed of 1 wt.% monoterpene, 4 wt.% of Imwitor^® 900K as a solid lipid and 2.5 wt.% of Poloxamer188 as a surfactant. Empty SLN consisted of 5 wt.% of Imwitor^® 900K and 2.5 wt.% of Poloxamer188. The mean particles size (Z-Ave) and polydispersity index (PDI) of SLN were analyzed by dynamic light scattering (DLS), while the zeta potential (ZP) of each formulation were measured by electrophoretic light scattering. LUMiSizer^® was applied to calculate the velocity distribution in the centrifugal field and instability index. Drug release profile from SLN was analyzed using Franz cell diffusion cells assayed by UV–Vis spectrophotometry, whereas the gas chromatography technique was applied to determine the encapsulation parameters of volatile monoterpenes. The matrix state, polymorphism and phase behavior of SLN were studied by X-ray diffraction (XRD, low and wide angles) and differential scanning calorimetry (DSC). Selected monoterpenes were successfully loaded in glycerol monostearate SLN. A burst release profile within the first 15 min was observed for all formulations, being the modified release profile dependent on the type of monoterpene and on the encapsulation efficiency.

The reversible redox conversion of nitrite and nitric oxide ((•)NO) in a physiological setting is now widely accepted. Nitrite has long been identified as a stable intermediate of (•)NO oxidation but several lines of evidence support the reduction of nitrite to nitric oxide in vivo. In the gut, this notion implies that nitrate from dietary sources fuels the longstanding production of nitrite in the oral cavity followed by univalent reduction to (•)NO in the stomach. Once formed, (•)NO boosts a network of reactions, including the production of higher nitrogen oxides that may have a physiological impact via the post-translational modification of proteins and lipids. Dietary compounds, such as polyphenols, and different prandial states (secreting specific gastric mediators) modulate the outcome of these reactions. The gut has unusual characteristics that modulate nitrite and (•)NO redox interplay: (1) wide range of pH (neutral vs acidic) and oxygen tension (c.a. 70 Torr in the stomach and nearly anoxic in the colon), (2) variable lumen content and (3) highly developed enteric nervous system (sensitive to (•)NO and dietary compounds, such as glutamate). The redox interplay of nitrite and (•)NO might also participate in the regulation of brain homeostasis upon neuronal glutamatergic stimulation in a process facilitated by ascorbate and a localized and transient decrease of oxygen tension. In a way reminiscent of that occurring in the stomach, a nitrite/(•)NO/ascorbate redox interplay in the brain at glutamatergic synapses, contributing to local (•)NO increase, may impact on (•)NO-mediated process. We here discuss the implications of the redox conversion of nitrite to (•)NO in the gut, how nitrite-derived (•)NO may signal from the digestive to the central nervous system, influencing brain function, as well as a putative ascorbate-driven nitrite/NO pathway occurring in the brain.

Resveratrol (RSV) is a natural antioxidant commonly found in grapes, berries, and nuts that has shown promising results in the treatment of a variety of degenerative and age-related diseases. Despite the proven beneficial results on reduction of reactive oxidant species (ROS) and on inflammatory process, RSV shows various limitations including low long-term stability, aqueous solubility, and bioavailability, restricting its applications in the medical-pharmaceutical area. To overcome these limitations, it has been applied in pharmaceutical formulations as nanostructured lipid carriers (NLC). Thus, the present study focuses on the optimization of the production process of NLC. NLC was produced by high shear homogenization (HSH) and ultrasound method (US) using Compritol^® ATO C888 as solid lipid and Miglyol 812^® as liquid lipid. In order to obtain an optimized formulation, we used a 2² full factorial design with triplicate of central point investigating the effects of the production process parameters; shear intensity and homogenization time, on the mean particle size (PS) and polydispersity index (PDI). Instability index, encapsulation efficiency, and production yield were also evaluated. As the PS and PDI values obtained with 6 min of shear at 19,000 rpm and 10 min of shear and 24,000 rpm were similar, the instability index (<0.1) was also used to select the optimal parameters. Based on the results of the experimental design and instability index, it was concluded that the shear rate of 19,000 rpm and the shear time of 6 min are the optimal parameters for RSV-loaded NLC production. Factorial design contributed therefore to optimize the variables of the NLC production process from a small number of experiments.