Lipid-based nanocarriers provide versatile platforms for the encapsulation and delivery of many different bioactive compounds to improve the solubility, stability and therapeutic efficacy of bioactive phyto-compounds. In this study, liposomes were used to load leaf extract of Coffea Arabica, which is known to be rich beneficial substances such as alkaloids, flavonoids, etc. The aim of this work is to optimize the valorization of agricultural wastes containing natural antioxidants. The physico-chemical properties of the liposomes loaded with chlorogenic acid or Coffea arabica leaf extract were evaluated. The average size of empty and loaded liposomes was found to range of 120-150 nm, which is consistent with the fact that the addition of chlorogenic acid or Coffea arabica leaf extract can change the average size of the vesicles without affecting the physicochemical properties of the lipid bilayer, which remain stable systems. A structural and morphological characterization as well as an evaluation of biological properties such as viability in normal human dermal fibroblasts, is also been carried out. The cationic liposomes show a good average size and low polydispersity index values, indicating that the liposomes tend to be monodisperse and therefore stable. In particular, DOPC/DOTAP liposomes generally have better properties than DOPC/DDAB liposomes for use as encapsulation systems for natural plant extracts.

New graft copolymers were prepared by reaction of poly (vinyl alcohol) (PVA) with mono-imidazolide or bis-imidazolide derivatives of ferulic acid (FA) with the formation of ester bonds. The obtained graft copolymers, thanks to the crosslinking capability of FA, formed in water strong gels as verified by rheological analyses. The resulting hydrogels were characterized to evaluate their applicability as wound dressing. In this perspective, their capability to absorb and retain a large amount of fluid without dissolving was verified by swelling kinetics and Moisture Vapour Transmission Rate measurements. Their stability towards mechanical solicitations was assessed by quantifying elasticity, compliance, stress-relaxation, and adhesivity properties. The analyses pointed out that hydrogel PVA-FA2-3 obtained by feruloylation of PVA with bis-imidazole derivative of ferulic acid using an acylation agent/polymer molar ratio 0.03/1 resulted the best candidate for the foreseen application.

Consumption of cereals (and particularly ancient cereals) is considered the base of a healthy diet, and all current dietary guidelines have cereals at the bottom of the nutrition pyramid. Together with cereals, legumes are an excellent source of nutrients and nutraceuticals. The effects of agroindustrial pretreatments (flaking and precooking processes) on the antioxidant potential of flours from ancient cereals and legumes were studied. The extraction of free hydrophilic phenolic compounds was carried out in a hydroalcoholic solvent mixture via an ultrasound-assisted process. Furthermore, the solid residue was successively hydrolyzed by an alkaline solution to extract the bound phenolic fraction. Both free and bound extracted fractions were then quantitatively characterized for total polyphenolic and flavonoid contents, and the antioxidant potential was determined by carrying out the ABTS and DPPH radical scavenging assays, expressing the results (in both cases) as the Trolox equivalent antioxidant capacity (TEAC/ABTS and TEAC/DPPH, respectively). The samples were also extracted in organic apolar solvents (acetone or water-saturated iso-butanol) to quantitatively characterize lipophilic antioxidant compounds and pigments. A discussion on the comparison of these analytical parameters of flours obtained from raw, flaked, and precooked cereals and legumes is reported revealing that (i) phenolic compounds are mainly present in the post-hydrolysis extract (bound fraction), (ii) the precooking process significantly reduced the concentration of antioxidants, (iii) the flaking process slightly increased the phenolic content, (iv) legumes were less influenced by pretreatments, suggesting the possibility of using legumes to enrich cereal foods.

An easy and viable crosslinking procedure by click-chemistry (click-crosslinking) of hyaluronic acid (HA) was developed. In particular, the clickable propargyl groups of hyaluronane-based HA-FA-Pg graft copolymers showing low and medium molecular weight values were exploited in crosslinking by click-chemistry by using a hexa(ethylene glycol) spacer. The resulting HA-FA-HEG-CL materials showed an apparent lack of in vitro cytotoxic effects, tuneable water affinity, and rheological properties according to the crosslinking degree that suggests their applicability in different biomedical fields.

Coffea arabica L. leaves represent a viable alternative to the canonical matrices used for preparation of beverages, such as tea leaves and grounded coffee beans. Coffee leaves infusions are rich in antioxidant phenolic compounds and have a lower concentration of caffeine. Due to increasing interest in this field, a complete study of the bioactive compounds as chlorogenic acids, xanthones and alkaloids is noteworthy. C. arabica leaves were subjected to ultrasound-assisted extraction, and the extracts were studied via nuclear magnetic resonance spectroscopy (NMR) and chromatographic techniques coupled with mass spectrometry (HPLC-MSn) to identify and quantify the secondary metabolites profile through an untargeted data dependent approach. A quantitative analysis was performed for the major components—chlorogenic acids, mangiferin, caffeine and trigonelline—via HPLC-MS in Single Ion Monitoring (SIM) mode. In total, 39 compounds were identified. The presence of these bioactive compounds proved the strong potential of C. arabica leaves as functional food and as an alternative to classic infused beverages.

Prunus persica L. is one of the most important fruit crops in European production, after grapes, apples, oranges and watermelons. Most varieties are rich in secondary metabolites, showing antioxidant properties for human health. The purpose of this study was to develop a chemical analysis methodology, which involves the use of different analytical-instrumental techniques to deepen the knowledge related to the profile of metabolites present in selected cultivars of peaches and nectarines cultivated in the Mediterranean area (Southern Italy). The comparative study was conducted by choosing yellow-fleshed peaches (RomeStar, ZeeLady) and yellow-fleshed nectarines (Nectaross, Venus) from two geographical areas (Piana di Sibari and Piana di Metaponto), and by determining the chemical parameters for the flesh and skin that allow for identification of any distinctive varietal and/or geographical characteristics. A combined analytical and chemometric approach was used, trough rheological, thermogravimetric (TGA), chromatographic (HPLC-ESI-MS), spectroscopic (UV-Vis, ATR-FTIR, NMR) and spectrometric (ToF-SIMS) analysis. This approach allowed us to identify the characterizing parameters for the analysis of a plant matrix so that the developed methodology could define an easily exportable and extendable model for the characterization of other types of vegetable matrices.

Various antioxidant substances have a protective effect on the skin when applied in suitable formulations. Natural lycopene (extracted from tomato), incorporated in an oil/water emulsion at a concentration of 0.03% and applied to the skin 30 min before ultraviolet exposure, decreased the erythema induced by UV radiation. Lycopene was more effective when associated with α-tocopherol palmitate and ascorbic acid, at concentrations of 0.5% and 1%, respectively. Since lycopene does not screen UV radiation, its protective ability is due to antioxidant activity. The potentiation of its effectiveness by vitamins E and C can probably be attributed to an interaction between the three substances in the cascade of events leading to the antiradical effect. As proposed for β-carotene, lycopene may act by repairing the tocopherol radical, after which it is repaired by the ascorbic acid. The efficiency of the system could be related to the different affinities (lipophilic or hydrophilic) of the components of this triple association. Because of its characteristics, lycopene is particularly suitable for topical application in sunscreens or in any preparation designed to prevent or reduce the harmful effects of oxidative stimuli.

Polybenzofulvenes are π-stacked polymers, which can be synthesized by spontaneous polymerization of the corresponding monomers without the use of catalysts or initiators. Therefore, they can be obtained completely free from byproducts, impurities, or harmful substances. The absence of any relevant toxic effects and cell viability impairments allows PEGylated polybenzofulvene brushes to be potentially functional in a wide range of biological, biomedical, and biotechnological applications. Moreover, the properties of these polymers, in terms of interaction with pharmacological active agents and the ability to self-assemble into nanoaggregates or a quite compact physical gel useful as drug delivery systems (DDSs), can be controlled by varying side chain moieties. Owing to the important role played by self-assembling DDS in the fields of the material and life sciences, the interaction and the delivery ability of polybenzofulvene polymers with model drug or protein molecules was definitively demonstrated. The present paper reviews the applications of polybenzofulvene derivatives in the drug delivery of a range of different drug molecules ranging from small molecules to peptides and proteins.

SummaryAimsWe recently described multifunctional tools (2a–c) as potent inhibitors of human Cholinesterases (ChEs) also able to modulate events correlated with Aβ aggregation. We herein propose a thorough biological and computational analysis aiming at understanding their mechanism of action at the molecular level.MethodsWe determined the inhibitory potency of 2a–c on Aβ1–42 self‐aggregation, the interference of 2a with the toxic Aβ oligomeric species and with the postaggregation states by capillary electrophoresis analysis and transmission electron microscopy. The modulation of Aβ toxicity was assessed for 2a and 2b on human neuroblastoma cells. The key interactions of 2a with Aβ and with the Aβ‐preformed fibrils were computationally analyzed. 2a–c toxicity profile was also assessed (human hepatocytes and mouse fibroblasts).ResultsOur prototypical pluripotent analogue 2a interferes with Aβ oligomerization process thus reducing Aβ oligomers‐mediated toxicity in human neuroblastoma cells. 2a also disrupts preformed fibrils. Computational studies highlighted the bases governing the diversified activities of 2a.ConclusionConverging analytical, biological, and in silico data explained the mechanism of action of 2a on Aβ1–42 oligomers formation and against Aβ‐preformed fibrils. This evidence, combined with toxicity data, will orient the future design of safer analogues.

Combination of dopamine D3 antagonism, serotonin 5-HT1A partial agonism, and antagonism at 5-HT2A leads to a novel approach to potent atypical antipsychotics. Exploitation of the original structure-activity relationships resulted in the identification of safe and effective antipsychotics devoid of extrapyramidal symptoms liability, sedation, and catalepsy. The potential atypical antipsychotic 5bb was selected for further pharmacological investigation. The distribution of c-fos positive cells in the ventral striatum confirmed the atypical antipsychotic profile of 5bb in agreement with behavioral rodent studies. 5bb administered orally demonstrated a biphasic effect on the MK801-induced hyperactivity at dose levels not able to induce sedation, catalepsy, or learning impairment in passive avoidance. In microdialysis studies, 5bb increased the dopamine efflux in the medial prefrontal cortex. Thus, 5bb represents a valuable lead for the development of atypical antipsychotics endowed with a unique pharmacological profile for addressing negative symptoms and cognitive deficits in schizophrenia.

Pimecrolimus is a drug belonging to the class of macrolactamic immunosuppressants, similar to tacrolimus, and has been employed mainly in the treatment of atopic dermatitis, but is also active in other skin diseases, including genital lichen sclerosus (LS). The safety profile of pimecrolimus was the subject of special attention by the US FDA, which in 2005 issued a Public Health Advisory on the potential risk of cancer associated with the use of topical calcineurin inhibitors. However, many scientific societies have criticized the FDA note, referring to the vast literature on the subject in which there is no evidence available that topical use of the drug is dangerous. Patients with LS, of both sexes, may develop genital squamous cell carcinoma. This event, however, is not a contraindication to the use of pimecrolimus.

The production of sunscreens is regulated by laws and lists, constantly updated on the basis of scientific information. Most advanced countries have regulatory bodies that publish and update the list of authorized substances. Inorganic filters, zinc oxide and titanium dioxide are often used as nanostructured forms. Nanoparticles have been the subject of technological studies aimed at improving efficacy and safety. The organic ingredients are able to absorb UV radiation on a selective or broad spectrum. The latter is preferable given the role of UVA radiation in skin carcinogenesis. The organic filters may interact with epidermal proteins and induce sensitization. They can also be absorbed, causing systemic effects. In addition, some organic ingredients, such as avobenzone, may undergo photodegradation, needing special formulation requirements.

Skin cancer incidence is continuously increasing, and sun exposure has been indicated as the primary cause of such an explosion in prevalence. The phenom-enon is particularly pronounced among Caucasians living in developed countries, suggesting that some changes in lifestyle may be the main trigger. Generally, most people consider suntan as a sign of physi-cal and social wellbeing, and the desire to acquire a suntan has promoted holidays in sunny countries, also out of season. Furthermore, the use of artificial tanning devices that emit UVA/UVB radiation has become increasingly popular among young people, especially females.In this scenario a change of direction can be obtained by education on the cor-rect way to enjoy sun exposure from child-hood, but this requires a large organiza-tional effort, which is difficult to achieve in a short time. In the immediate future, the implementation of cutaneous photo-protection appears more feasible. In fact, the large-scale use of products able to neu-tralize the UV radiation has been advo-cated by many international institutions as the most appropriate means to reduce skin damage from solar radiation, namely photoaging and photocarcinogenesis.The photoprotection products have to provide evidence of protective ability against solar radiation and, simultane-ously, given their wide use, must be toxi-cologically safe. Both these requirements are encompassed by the current laws that provide lists of permitted substances. Achieving these goals has required, and still requires, great effort in identifying suitable ingredients and technologically advanced and safe formulations.This special focus issue on ‘Sunscreens and photoprotection’ highlights recent advances in the technology of products, and also provides an update on the main dermatological pathologies that could be prevented with photoprotection.The issue begins with an editorial by Friedman

We compared the ability of pure lycopene (Lyco) versus lycopene phytocomplex (LycoC) to induce apoptosis in vitro. We found that LycoC, but not Lyco, was able to trigger apoptosis in HL60 cells, as documented by subdiploid DNA content and phosphatidylserine exposure. LycoC-induced apoptosis was associated with reactive oxygen species (ROS) generation and loss of mitochondrial transmembrane potential, suggesting that LycoC triggered apoptosis via a mitochondrial pathway. We also verified the redox state of cells by measuring glutathione (GSH) content, but only a small percentage of cells showed GSH depletion, suggesting that the loss of GSH may be a secondary consequence of ROS generation. Moreover, LycoC pretreatment effectively increased apoptosis induced by photodynamic therapy (PDT), a mode of cancer treatment using a photosensitizer and visible light. LycoC pretreatment was even more potent in improving PDT than pretreatment with ascorbic acid or alpha-tocopherol (or the two combined). Our results demonstrate that LycoC has a stronger cytotoxic effect than Lyco and is a better source of agents able to trigger apoptosis in HL60 cells and improve the efficacy of PDT in vitro.

Cosmetics are widely used products, and some, such as detergents for personal hygiene, can be considered indispensable. For this reason, they should not be toxic or irritating. Much attention has been devoted to research into surfactants, the major component of personal hygiene and domestic cleaning products. Although the latter are not cosmetics, they are similar to personal hygiene products and constitute a large class of potential irritants.Tolerance of irritants depends on many factors, which are not yet completely under-stood. Subjects with so-called sensitive skin may have variable reactivity, and clinical experience, as well as knowledge of skin biology, are necessary to recognize such indi-viduals. Dermatologists have a fundamental role in identifying individuals at risk for skin irritation and providing information useful to develop mild products.

Aim of this work was the study of ferulic acid/cyclodextrin (CD) association complexes. Ferulic acid (FA) is a compound well-known as antioxidant and photoprotective agent (approved in Japan as sunscreen). Notwithstanding this, it is poorly suited for cosmetic applications because it undergoes functional and organoleptic modifications, when it is exposed to air, UV-light and heat. For this reason we prepared a set of FA/CD complexes with the aim to improve its physico-chemical stability. The inclusion complexes were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), and nuclear magnetic resonance ( 1 H-NMR). The FA/α-CD complex showed the most promising properties (high association constant, high degree of photostability, slower FA release) as sunscreen delivery system.

Ferulic acid (FA) is a highly effective antioxidant and photo-protective agent, already approved in Japan as a sunscreen, but it is poorly suited for cosmetic application because of its low physicochemical stability. We prepared the inclusion complex of FA with α-cyclodextrin by co-precipitation from an aqueous solution, and used 1H NMR and molecular dynamics to investigate the most probable structure of the inclusion complex. In rotating frame nuclear Overhouser effect spectroscopy (ROESY) experiments FA penetrated the α-CD hydrophobic cavity with the α,β-unsaturated part of the molecule and some of its aromatic skeleton. In proton chemical shift measurements of FA and α-cyclodextrins we determined the stoichiometry of the association complex (1:1) by Job's method, and its stability constant (K1:1 1162±140M−1) and described the molecular dynamics of the complex on the basis of theoretical studies. Encapsulation with α-cyclodextrin improves (i) the chemical stability of FA against UVB stress (10 MED [Minimal Erythemal Dose: 1 MED=25mJ/cm2 for skin phototype II: 30]), since no degradation products are formed after irradiation, and (ii) the bioavailability of FA on the skin, slowing its delivery (Strainer cell model).