In recent decades, mass spectrometry techniques, particularly when combined with separation methods such as high-performance liquid chromatography, have become increasingly important in pharmaceutical, bio-analytical, environmental, and food science applications because they afford high selectivity and sensitivity. However, mass spectrometry has limitations due to the matrix effects (ME), which can be particularly marked in complex mixes, when the analyte co-elutes together with other molecules, altering analysis results quantitatively. This may be detrimental during method validation, negatively affecting reproducibility, linearity, selectivity, accuracy, and sensitivity. Starting from literature and own experience, this review intends to provide a simple guideline for selecting the best operative conditions to overcome matrix effects in LC-MS techniques, to obtain the best result in the shortest time. The proposed methodology can be of benefit in different sectors, such as pharmaceutical, bio-analytical, environmental, and food sciences. Depending on the required sensitivity, analysts may minimize or compensate for ME. When sensitivity is crucial, analysis must try to minimize ME by adjusting MS parameters, chromatographic conditions, or optimizing clean-up. On the contrary, to compensate for ME analysts should have recourse to calibration approaches depending on the availability of blank matrix. When blank matrices are available, calibration can occur through isotope labeled internal standards and matrix matched calibration standards; conversely, when blank matrices are not available, calibration can be performed through isotope labeled internal standards, background subtraction, or surrogate matrices. In any case, an adjusting of MS parameters, chromatographic conditions, or a clean-up are necessary.

We are now seeing an increase in the production of agri-food waste, which is an essential resource for the recovery of bioactive compounds that may be employed as innovative natural ingredients in cosmetics. To date, the approach to cosmetics preservation has seen a significant shift in the search for biological components that give healthier alternatives for customers and help businesses operate in an environmentally friendly manner. To achieve this goal, we studied pomegranate extracts using the peel and, for the first time, extracts from the male flowers of a wide pomegranate variety cultivated in the Marche region, specifically, the Wonderful, Mollar de Elche, Parfianka, and less-studied G1 varieties. We studied the phenol compounds profile, antioxidant capacity, antimicrobial activity, and cell viability of the obtained pomegranate extracts. The identification and quantification of phenol compounds belonging to different classes, such as hydrolysable tannins, hydroxybenzoic acid, hydroxycinnamic acid, dihydroflavonol, gallocatechin, and anthocyanins, were performed using UPLC-ESI-MS/MS. Punicalagin isomers and punicalin resulted in the most abundant polyphenols found in the peel and male flower extracts. Mollar de Elche 2020 peel extract revealed a high concentration of punicalagin A and B (7206.4 mg/kg and 5812.9), while the content of gallic acid revealed high results in the G1 and Parfianka varieties. All extracts were spectrophotometrically analysed to determine their total phenol content (TPC) using the Folin–Ciocalteu method and their antioxidant capacity (AC). In terms of the total phenol obtained by the Folin–Ciocalteu colorimetric method, Mollar de Elche 2020 extracts reported the highest TPC content of 12.341 µmol GAE/g. Results revealed that the Mollar de Elche and Wonderful 2020 peel extracts demonstrated the highest TPC and AC. Furthermore, AC results indicated that the peel extracts displayed higher AC than the male flower extract due to the high punicalagin content detected by UPLC analysis. The antimicrobial activity testing revealed that the Wonderful and G1 2020 peel extracts resulted active against Escherichia coli, while all extracts exhibited promising anticandidal activity. Additionally, the cytocompatibility was evaluated in keratinocytes HaCaT cells by testing concentrations of pomegranate extracts ranging from 0.15 to 5.00 mg/mL. Extracts were non-toxic for the cells in the tested concentration range. The acquired results may help exploit pomegranate agri-food waste products provided by the Marche region’s short supply chain for their use as an antimicrobial and antioxidant booster in the formulation of cosmetic products.

This project aimed to apply eco-friendly extraction methods to Crocus sativus L. by-product (flowers without stigmas i.e., tepals composed of petals and sepals) to recover extracts with high antioxidant capacity and polyphenol content, to be used in cosmetic products. Flowers grown in two different Italian regions (Sample 1—Alba in Piemonte, north of Italy and Sample 2—Sibillini in Marche, centre of Italy) were subjected for the first time to different eco-friendly microwave-mediated green solvents extractions (MGSE) andquali-quantitative determination in antioxidant molecules. Firstly, the extracts from Sample 1 were selected according to their total phenol content (TPC) by Folin–Ciocalteu’s assay and antioxidant capacity (AC) by spectrophotometric assays. Then, according to preliminary results, MGSE carried out in ethanol 70°, water, and glycerin were selected as the most performing methods and applied to both Samples 1 and 2. The best results were obtained using green solvents, such as water or ethanol 70°, for the samples coming from Marche. The identification and quantification of phenolic compounds, belonging to anthocyanins and flavonols classes, was performed by using UPLC-DAD-ESI-MS. Concerning flavonols content, the most abundant analyte is kaempferol 3-O-sophoroside and the extract in water from Sample 1 showed the higher amount of flavonols, reaching the concentration of 25.35 mg of kaempferol 3-O-glucoside equivalent per gram of tepals DW of raw material. Among anthocyanins, the most abundant was delphinidin 3,5-O-diglucoside and the high concentration of anthocyanin was detected in water and ethanol extract. Two new compounds, myricetin-di-glucoside and primflasine, were identified for the first time in Crocus sativus L. by-product by high-resolution mass spectrometry (HRMS). The green batches obtained by extraction were thus characterized and evaluated for their biological potential and safety in keratinocyte HaCaT cells. The extracts were not cytotoxic up to 0.03 mg/mL. The water and ethanol 70° extracts were the most effective in counteracting oxidative stress induced by H2O2 and UVA exposure and reduced cytotoxicity induced by UVB exposure. The water extract was also able to significantly reduce cytotoxicity induced by sodium dodecyl sulphate-induced damage. Taken together, these results suggest a potential use of these waste materials as cosmeceutical preparations such as antiaging, and as anti-skin irritation formulation by-products.

A redox-responsive nanocarrier is a promising strategy for the intracellular drug release because it protects the payload, prevents its undesirable leakage during extracellular transport, and favors site-specific drug delivery. In this study, we developed a novel redox responsive core-shell structure nanohydrogel prepared by a water in oil nanoemulsion method using two biocompatible synthetic polymers: vinyl sulfonated poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate)-polyethylene glycol-poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate) triblock copolymer, and thiolated hyaluronic acid. The influence on the nanohydrogel particle size and distribution of formulation parameters was investigated by a three-level full factorial design to optimize the preparation conditions. The surface and core-shell morphology of the nanohydrogel were observed by scanning electron microscope, transmission electron microscopy, and further confirmed by Fourier transform infrared spectroscopy and Raman spectroscopy from the standpoint of chemical composition. The redox-responsive biodegradability of the nanohydrogel in reducing environments was determined using glutathione as reducing agent. A nanohydrogel with particle size around 250 nm and polydispersity index around 0.1 is characterized by a thermosensitive shell which jellifies at body temperature and crosslinks at the interface of a redox-responsive hyaluronic acid core via the Michael addition reaction. The nanohydrogel showed good encapsulation efficiency for model macromolecules of different molecular weight (93% for cytochrome C, 47% for horseradish peroxidase, and 90% for bovine serum albumin), capacity to retain the peroxidase-like enzymatic activity (around 90%) of cytochrome C and horseradish peroxidase, and specific redox-responsive release behavior. Additionally, the nanohydrogel exhibited excellent cytocompatibility and internalization efficiency into macrophages. Therefore, the developed core-shell structure nanohydrogel can be considered a promising tool for the potential intracellular delivery of different pharmaceutical applications, including for cancer therapy.