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In the present study, a tangential membrane filtration system was applied to recover phenols from olive mill wastewater. The obtained concentrates were characterised for physico-chemical traits, antioxidant activity and antimicrobial effects. Results indicated that the highest concentration of hydroxytyrosol (7203.7 mg/L) was detected in the concentrate obtained by reverse osmosis, which also showed the highest antioxidant and antimicrobial activity. Moreover, the same concentrate was added, at different ratio, up to 4:250 v/v, into a commercial blood orange juice. The fortified juice with the addition of the concentrate, up to 2:250 v/v ratio, did not show off-flavour and off-odour compared to the control. Furthermore, after 60 days of refrigerated storage, the fortified juice exhibited a hydroxytyrosol content still complying with the daily intake recommended by EFSA health claim. The obtained results can be industrially useful in producing orange juice added with a natural antioxidant concentrate as a 'clean label' ingredient.

The difficulties encountered in the treatment of brain diseases with conventional pharmacological tools have created the need for innovative strategies. The combination of nanocarriers and alternative administration routes could represent an efficient approach to reach the brain. Intranasal administration (IN) provides a non-invasive option to deliver drugs to the brain, bypassing the BBB, reducing the first-pass effect and enhancing patient compliance. The objective of the present study was to investigate the biodistribution and bioavailability to the brain of polymeric nanoparticles (PNPs) after IN administration in healthy mice. PNPs were prepared with poly-lactide-co-glycolide polymer using nanoprecipitation method. PNPs had a polymodal distribution around 350 nm. The biodistribution of DiR-loaded PNPs was evaluated by means of 3D fluorescence tomography imaging. Our results show that 3h after a single IN administration, more than 5% of the injected dose was detectable in the brain. PNPs were quickly cleared from the thorax and the abdominal cavity, while the brain fluorescence slowly decreased ranging from 3.7% to 2.3% between 24h and 96h. Repeated IN administrations (2 administrations, 24h apart) provided a significant increment of PNPs-associated fluorescence in the brain, without affecting PNPs accumulation in other organs. These findings support nose-to-brain translocation of PNPs as a noninvasive strategy to enhance the bioavailability of therapeutics to the brain

Nose to brain delivery, combining with polymeric nanocarriers (NPs), represents a promising non-invasive strategy to carry molecules into the brain, bypassing blood brain barrier. It's possible to increase the residence time against mucociliar clearance and to prolong the release in the target site, with appropriate NPs. We used spherical NPs with negative surface charge and with a mean size lower 250 nm suitable for nose to brain delivery. To detect the cellular distributions of NPs, a fluorescent neural marker, rhodamine B, was encapsulated into NPs observed on a fluorescence microscope. The aim of this study was to investigate in the rat the brain localization of the fluorescent NPs 8, 24 and 48 h after IN administration. Our data demonstrated that the NPs could be internalized into cells and their internalization was time and region dependent. In fact, within the initial 8 h, many fluorescence NPs were found around the cells. With the extension of time, the intracellular labeled NPs increased with regional differences in the brain. In fact, after 24 h the uptake of labeled NPs was prevalently found in the rostral regions, whereas after 48 h the uptake of the labeled NPs decreased in the rostral and increased in caudal regions of the brain. These findings support the hypothesis that therapeutic agents loaded NPs, utilized in this study, may have a direct access to the brain and can represent a very promising strategy for the diseases of the central nervous system.

In the U87-MG glioma cell line we assessed the effect of unloaded/NLC-loaded FA on the TG2-mediated apoptotic pathway activation, and cell cycle progression.

The nasal route has received a great deal of attention as a convenient and reliable method for the brain target on administration of drugs. When drugs are loaded into nanoparticles (NPs) the interaction with mucosa transports directly into the brain, skipping the blood- brain barrier and achieving rapid cerebrospinal fluid levels. Poly-lactic acid (PLA), poly-lactic-co-glycolic acid (PLGA), and chitosan (CS) were chosen to prepare NPs. After optimization of CS nanocarriers, our goal was to evaluate the different type of NPs uptake into olfactory ensheathing cells (OECs). We then correlated obtained biological data to zeta potential measurements of cells treated with NPs. Rodhamine-loaded NPs were used to study the uptake of OECs carried out by confocal microscopy at different times (1, 2, and 4 h). Our results showed that uptake of rodhamine-NPs by OECs was time dependent and it was influenced by the carrier charge. Confocal imaging of OECs demonstrated that NPPLGA showed a higher increase in uptake compared with NPPLA and NPCS after 1 h and it increased at 2-4 h. Zeta potential values of treated cells were more amplified with respect to untreated cells. The highest values were showed by unloaded NPPLGA, confirming microscopy data.