Editorial for Special Issue: "Recent Advances in Green Solvents".

Today, environmental conservation is one of the most urgent targets [...].

Alginate-Chitosan Membranes for the Encapsulation of Lavender Essential Oil and Development of Biomedical Applications Related to Wound Healing.

Biopolymers such as chitosan (CHT) or alginate (ALG) are among the most prominent for health-related applications due to their broad bioactivity. Their combination for the preparation of membranes is hereby proposed as an application for wound healing with the incorporation of lavender essential oil (LEO), widely known for its antioxidant and antimicrobial properties. The preparation of CHT, CHT + LEO, ALG, ALG + LEO, and CHT/ALG + LEO membranes was accomplished, and its composition was analyzed using Fourier Transform Infrared Spectroscopy (FTIR). The water absorption capacity and oil release profile of the membranes revealed higher water uptake capacity when a lower LEO release was obtained. The combined CHT/ALG + LEO film showed a water uptake percentage of 638% after 48 h and a maximum LEO release concentration of 42 mg/L. Cytotoxicity and biocompatibility of the prepared membranes were studied using a HaCaT cell line, with an assessment of cell viability regarding film leachables, DNA quantification, and DAPI-phalloidin staining. The results revealed that the indirect contact of the prepared membranes via its leachables does not compromise cell viability, and upon direct contact, cells do not adhere or proliferate on the surface of the membranes. Moreover, the CHT/ALG + LEO membrane increases cell proliferation, making it suitable for applications in wound healing.

Selective extraction and stabilization of bioactive compounds from rosemary leaves using a biphasic NADES.

Rosemary (Rosmarinus officinalis) is a natural source of bioactive compounds that have high antioxidant activity. It has been in use as a medicinal herb since ancient times, and it currently is in widespread use due to its inherent pharmacological and therapeutic potential, in the pharmaceutical, food, and cosmetic industries. Natural deep eutectic systems (NADESs) have recently been considered as suitable extraction solvents for bioactive compounds, with high solvent power, low toxicity, biodegradability, and low environmental impact. The present work concerns the extraction of compounds such as rosmarinic acid, carnosol, carnosic acid, and caffeic acid, from rosemary using NADESs. This extraction was carried out using heat and stirring (HS) and ultrasound-assisted extraction (UAE). A NADES composed of menthol and lauric acid at a molar ratio of 2:1 (Me:Lau) extracted carnosic acid and carnosol preferentially, showing that this NADES exhibits selectivity for nonpolar compounds. On the other hand, a system of lactic acid and glucose (LA:Glu (5:1)) extracted preferentially rosmaniric acid, which is a more polar compound. Taking advantage of the different polarities of these NADESs, a simultaneous extraction was carried out, where the two NADESs form a biphasic system. The system LA:Glu (5:1)/Men:Lau (2:1) presented the most promising results, reaching 1.00 ± 0.12 mg of rosmarinic acid/g rosemary and 0.26 ± 0.04 mg caffeic acid/g rosemary in the more polar phase and 2.30 ± 0.18 mg of carnosol/g of rosemary and 17.54 ± 1.88 mg carnosic acid/g rosemary in the nonpolar phase. This work reveals that is possible to use two different systems at the same time and extract different compounds in a single-step process under the same conditions. NADESs are also reported to stabilize bioactive compounds, due to their interactions established with NADES components. To determine the stability of the extracts over time, the compounds of interest were quantified by HPLC at different time points. This allows the conclusion that bioactive compounds from rosemary were stable in NADESs for long periods of time; in particular, carnosic acid presented a decrease of only 25% in its antioxidant activity after 3 months, whereas the carnosic acid extracted and kept in the methanol was no longer detected after 15 days. The stabilizing ability of NADESs to extract phenolic/bioactive compounds shows a great promise for future industrial applications.

Supercritical CO2 Assisted Impregnation of Ibuprofen on Medium-Chain-Length Polyhydroxyalkanoates (mcl-PHA).

In this work, we propose the utilization of scCO2 to impregnate ibuprofen into the mcl-PHA matrix produced by Pseudomonas chlororaphis subs. aurantiaca (DSM 19603). The biopolymer has adhesive properties, is biocompatible and has a melting temperature of 45 °C. Several conditions, namely, pressure (15 and 20 MPa) and impregnation time (30 min, 1 h and 3 h) were tested. The highest ibuprofen content (90.8 ± 6.5 mg of ibuprofen/gPHA) was obtained at 20 MPa and 40 °C, for 1 h, with an impregnation rate of 89 mg/(g·h). The processed mcl-PHA samples suffered a plasticization, as shown by the decrease of 6.5 °C in the Tg, at 20 MPa. The polymer's crystallinity was also affected concomitantly with the matrices' ibuprofen content. For all the impregnation conditions tested the release of ibuprofen from the biopolymer followed a type II release profile. This study has demonstrated that the mcl-PHA produced by P. chlororaphis has a great potential for the development of novel topical drug delivery systems.

New deep eutectic solvent assisted extraction of highly pure lignin from maritime pine sawdust (Pinus pinaster Ait.).

Lignocellulosic biomass is a renewable and sustainable feedstock, mainly composed of cellulose, hemicellulose, and lignin. Lignin, as the most abundant natural aromatic polymer occurring on Earth, has great potential to produce value-added products. However, the isolation of highly pure lignin from biomass requires the use of efficient methods during lignocellulose fractionation. Therefore, in this work, novel acidic deep eutectic solvents (DESs) were prepared, characterized and screened for lignin extraction from maritime pine wood (Pinus pinaster Ait.) sawdust. The use of cosolvents and the development of new DES were also evaluated regarding their extraction and selectivity performance. The results show that an 1 h extraction process at 175 °C, using a novel DES composed of lactic acid, tartaric acid and choline chloride, named Lact:Tart:ChCl, in a molar ratio of 4:1:1, allows the recovery of 95 wt% of the total lignin present in pine biomass with a purity of 89 wt%. Such superior extraction of lignin with remarkable purity using a "green" solvent system makes this process highly appealing for future large-scale applications.

Natural deep eutectic systems as alternative nontoxic cryoprotective agents.

Natural deep eutectic systems (NADES) are mostly composed of natural primary metabolites such as sugars, sugar alcohols, organic acids, amino acids and amines. These simple molecules have been identified in animals living in environments with extreme temperature amplitudes, being responsible for their survival at negative temperatures during winter. Herein, we report for the first time the use of NADES based on trehalose (Treh) and glycerol (Gly) in cryopreservation, as cryoprotective agents (CPA). The evaluation of the thermal behaviour of these eutectic systems, showed that NADES have a strong effect on the water crystallization/freezing and melting process, being able to reduce the number of ice crystals and hence ice crystal damage in cells, which is a crucial parameter for their survival, upon freezing. Using this NADES as CPA, it is possible to achieve similar or even better cellular performance when compared with the gold standard for cryopreservation dimethyl sulfoxide (DMSO). In this sense, this work relates the physical properties of the NADES with their biological performance in cryopreservation. Our comprehensive strategy results in the demonstration of NADES as a promising nontoxic green alternative to the conventional CPA's used in cryopreservation methods.

Design of controlled release systems for THEDES-Therapeutic deep eutectic solvents, using supercritical fluid technology.

Deep eutectic solvents (DES) can be formed by bioactive compounds or pharmaceutical ingredients. A therapeutic DES (THEDES) based on ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), and menthol was synthesized and its thermal behavior was analyzed by differential scanning calorimetry (DSC). A controlled drug delivery system was developed by impregnating a starch:poly-ϵ-caprolactone polymeric blend (SPCL 30:70) with the menthol:ibuprofen THEDES in different ratios (10 and 20 wt%), after supercritical fluid sintering at 20 MPa and 50 °C. The morphological characterization of SPCL matrices impregnated with THEDES was performed by scanning electron microscopy (SEM) and micro-computed tomography (micro-CT). Drug release studies were carried out in a phosphate buffered saline. The results obtained provide important clues for the development of carriers for the sustainable delivery of bioactive compounds.