Alzheimer’s disease (AD) is a neurodegenerative disorder associated with marked oxidative stress at the level of the brain. Recent studies indicate that increasing the antioxidant capacity could represent a very promising therapeutic strategy for AD treatment. Astaxanthin (AST), a powerful natural antioxidant, could be a good candidate for AD treatment, although its use in clinical practice is compromised by its high instability. In order to overcome this limit, our attention focused on the development of innovative AST-loaded stealth lipid nanoparticles (AST-SSLNs) able to improve AST bioavailability in the brain. AST-SSLNs prepared by solvent-diffusion technique showed technological parameters suitable for parenteral administration (<200 nm). Formulated nanosystems were characterized by calorimetric studies, while their toxicological profile was evaluated by the MTT assay on the stem cell line OECs (Olfactory Ensheathing Cells). Furthemore, the protective effect of the nanocarriers was assessed by a long-term stability study and a UV stability assay confirming that the lipid shell of the nanocarriers was able to preserve AST concentration in the formulation. SSLNs were also capable of preserving AST’s antioxidant capacity as demonstrated in the oxygen radical absorbance capacity (ORAC) assay. In conclusion, these preliminary studies outline that SSLNs could be regarded as promising carriers for systemic administration of compounds such as AST aimed at AD treatment.

Curcumin (CUR) has a wide range of pharmacological properties, including anti-inflammatory and antioxidant activities, and it can be considered a good candidate for the potential treatment of central nervous system (CNS) pathologies, although its use in clinical practice is compromised due to its high lipophilicity. Solid lipid nanoparticles (SLNs) are well-known nanocarriers representing a consolidated approach for the delivery of lipophilic compounds, but their systemic use is limited due their short half-life. The formulation of stealth SLNs (pSLNs) could be a valid strategy to overcome this limit. Curcumin-loaded-pSLNs were prepared by the solvent evaporation method. Formulation was characterized for their mean size, zeta potential, size distribution, and morphology. Drug antioxidant activity was evaluated by Oxygen Radical Absorbance Capacity (ORAC) assay. Finally, the obtained formulations were analyzed in terms of long-term stability. Curcumin-loaded-pSLNs showed good technological parameters with a mean particle size below 200 nm, as confirmed by TEM images, and a zeta potential value around −30 mV, predicting good long-term stability. Differential Scanning Calorimetry (DSC) analysis confirmed that PEG micelles interacted with the SLN surface; this suggests the location of the PEG on the pSLN surface. Therefore, these preliminary studies suggest that the produced formulation could be regarded as a promising carrier for the systemic administration.

(1) Background: For centuries, carob fruit has been used in the food field, while carob seeds have been mainly considered as food waste. Nowadays, there has been considerable attention toward the recovery of the waste plant matrices as possible sources of functional compounds with health properties. Therefore, our goal was to evaluate the health properties of carob seed extracts, and to study the effects of the ripening process on the chemical composition of the extracts. (2) Methods: After the mechanical separation of seeds from carob fruit, an ultrasound-assisted extraction (UAE) was performed to maximize and preserve the quality of bioactive compounds. Seed extracts were characterized by high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS) for the content of bioactive polyphenols, and were finally analyzed by oxygen radical absorbance capacity (ORAC), NO Scavenger (NO) and advanced glyoxidation end products (AGEs) assays, in order to estimate the antioxidant potential of the active compounds. (3) Results: Although both seed extracts of carob unripe (CAR-UR) and ripe (CAR-R) showed an interesting antioxidant activity, CAR-R had greater activity due to the procyanidins content. (4) Conclusions: Based on the obtained results, carob seed extracts could be regarded as interesting source of bioactive antioxidant compounds for a potential application in nutraceutical and food supplement fields.

Reactive oxygen and nitrogen species as well as advanced glycation endproducts (AGEs) and metalloproteinases (MMPs) play a key role in the development and progression of degenerative processes of body tissues, including skin. Natural antioxidant flavonoids could be beneficial in inhibiting AGEs’ formation and MMPs’ expression. In this study, the antioxidant activity of flavones (luteolin, apigenin, and chrysin) and flavonols (mirycetin, quercetin, and kaempferol) was compared with their inhibitory effects on both metalloproteinases’ (MMP-1, MMP-2, MMP-9, MMP-13) and AGEs’ formation. Comparisons were performed taking into account the hydroxyl group arrangement and the physico-chemical parameters the binding dissociation enthalpy (BDE), ionization potential (IP), partition coefficient (log P), and topological polar surface area (TPSA). Increasing the number of hydroxyl groups led to a proportional enhancement of antioxidant activity while an inverse relationship was observed plotting the antioxidant activity vs. BDE and IP values. All flavonoids acted as AGEs, MMP-1, and MMP-13 inhibitors, but they were less effective against MMP-2 and MMP-9. The inhibition of MMP-1 seemed to be related to the TPSA values while high TPSA and low log P values seemed important conditions for inhibiting MMP-13. Overall, our data suggest that an estimation of flavonoid activity could be anticipated based on their physico-chemical parameters.

Idebenone (IDE), a strong antioxidant widely investigated for the treatment of neurodegenerative diseases and skin disorders, shows low oral and topical bioavailability due to its unfavorable physico-chemical properties. In this work, to improve IDE topical effectiveness, we explored a two-steps approach: (1) we synthesized an IDE ester (IDEPCA) with pyroglutamic acid, a molecule whose hydrating effects are well known; (2) we loaded IDEPCA into solid lipid nanocarriers (SLN). We evaluated in vitro antioxidant and anti-glycation activity and in vivo hydrating effects after topical application in human volunteers from gel vehicles of IDEPCA SLN in comparison to IDE SLN. All SLN showed good technological properties (mean particle size < 25 nm, polydispersity index < 0.300, good stability). The oxygen radical absorbance capacity assay showed that IDEPCA SLN and IDE SLN had similar antioxidant activity while IDEPCA SLN were more effective in the in vitro NO scavenging assay. Both IDEPCA and IDE SLN showed the same effectiveness in inhibiting the formation of advanced glycation end products. In vivo experiments pointed out a better hydrating effect of IDEPCA SLN in comparison to IDE SLN. These results suggest that the investigated approach could be a promising strategy to obtain topical formulations with increased hydrating effects.

Resveratrol (RSV) is well known for its many beneficial activities, but its unfavorable physicochemical properties impair its effectiveness after systemic and topical administration; thus, several strategies have been investigated to improve RSV efficacy. With this aim, in this work, we synthesized a novel RSV triester with trolox, an analogue of vitamin E with strong antioxidant activity. The new RSV derivative (RSVTR) was assayed in vitro to evaluate its antioxidant and anti-glycation activity compared to RSV. RSVTR chemical stability was assessed at pH 2.0, 6.8, and 7.2 and different storage temperatures (5 °C, 22 °C, and 37 °C). An influence of pH stronger than that of temperature on RSVTR half-life values was pointed out, and RSVTR greatest stability was observed at pH 7.2 and 5 °C. RSVTR showed a lower antioxidant ability compared to RSV (determined by the oxygen radical absorbance capacity assay) while its anti-glycation activity (evaluated using the Maillard reaction) was significantly greater than that of RSV. The improved ability to inhibit the glycation process was attributed to a better interaction of RSVTR with albumin owing to its increased topological polar surface area value and H-bond acceptor number compared to RSV. Therefore, RSVTR could be regarded as a promising anti-glycation agent worthy of further investigations.