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Keywords = hydrophilic NADES

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24 pages, 4800 KiB  
Article
The Role of Natural Deep Eutectic Solvents in a Hydrogel Formulation Containing Lidocaine
by Feria Hasanpour, Mária Budai-Szűcs, Anita Kovács, Rita Ambrus, Orsolya Jójárt-Laczkovich, Boglárka Szalai, Branimir Pavlić, Péter Simon, Levente Törteli and Szilvia Berkó
Pharmaceutics 2025, 17(3), 324; https://doi.org/10.3390/pharmaceutics17030324 - 2 Mar 2025
Cited by 2 | Viewed by 1551
Abstract
Background/Objectives: This study investigates the use of natural deep eutectic solvents (NADESs) in enhancing the solubility and skin permeation of a lidocaine base, a lipophilic form, in hydrogel systems. The aim was to develop an environmentally sustainable and biocompatible alternative to conventional [...] Read more.
Background/Objectives: This study investigates the use of natural deep eutectic solvents (NADESs) in enhancing the solubility and skin permeation of a lidocaine base, a lipophilic form, in hydrogel systems. The aim was to develop an environmentally sustainable and biocompatible alternative to conventional lidocaine formulations, improving the dermal permeation and therapeutic efficacy. Methods: The lidocaine base was dissolved in a hydrophilic NADES system composed of choline chloride and citric acid, facilitating enhanced solubility, likely through new molecular interactions. Then, pH-adjusted hydrogels were formulated and optimized by employing a 32 full factorial design. Raman and nuclear magnetic resonance (NMR) spectroscopy were applied to evaluate the stability of lidocaine in the optimal formulation. The biopharmaceutical properties were investigated using in vitro drug release and skin permeation studies. In vivo tests assessed physiological skin parameters such as the hydration and transepidermal water loss. Results: The developed NADES-containing hydrogel significantly improved the solubility and stability of lidocaine. Skin permeation studies demonstrated enhanced dermal permeation compared with conventional hydrogel and ointment. These improvements, namely the enhanced solubility of lidocaine in the formulation and its increased permeation, were attributed to the dual effect of the NADES. Conclusions: NADES-containing hydrogels represent a promising green technology for formulating lidocaine-containing dermal preparations. This approach offers a biocompatible, natural-based alternative that can enhance the bioavailability and efficacy of topical anesthetics. Full article
(This article belongs to the Special Issue Transdermal Delivery: Challenges and Opportunities)
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16 pages, 4873 KiB  
Article
Evaluation of NADES for Pectin Films Reinforced with Oxalic Acid-Modified Chitin Nanowhiskers
by Andrea Mathilde Mebert, Cynthia Melisa Melian-Queirolo, Maria Fernanda Hamet, Guillermo Javier Copello and Andrea Gomez-Zavaglia
Polymers 2025, 17(5), 572; https://doi.org/10.3390/polym17050572 - 21 Feb 2025
Viewed by 613
Abstract
The effect of three NADESs as pectin film plasticizers was evaluated at 10%, 30%, and 50% w/w by using the casting method. Two hydrophilic (choline chloride with glycerol or citric acid) and one hydrophobic (thymol–camphor) NADESs were used as replacement for [...] Read more.
The effect of three NADESs as pectin film plasticizers was evaluated at 10%, 30%, and 50% w/w by using the casting method. Two hydrophilic (choline chloride with glycerol or citric acid) and one hydrophobic (thymol–camphor) NADESs were used as replacement for glycerol. Oxalic acid-modified chitin nanowhiskers (oCNWs) at 1% w/w were used to evaluate the effect of the NADESs on the nanofiller. The resulting films using the hydrophobic NADES were difficult to handle and prone to cracking and performed similarly to or worse than pure pectin films. As a result, they were not further evaluated. In contrast, the hydrophilic ones showed characteristics comparable to glycerol. It was found that films containing glycerol and choline chloride–glycerol NADESs showed a decrease in opacity and tensile strength and an increase in WVP, Young’s modulus, and maximum elongation. In contrast, those that contained citric acid exhibited a different behavior: opacity was less affected, and a decrease in WVP and an increase in tensile strength and Young’s modulus (at 10% and 30% plasticizer) were found. oCNWs tended to decrease WVP and increase Young’s modulus but not in a very significant way. Our findings demonstrate that NADESs can be used as plasticizers in pectin films without the need to include glycerol and that the nature of NADESs is relevant to tuning the final properties. Full article
(This article belongs to the Special Issue Sustainable Polymer Chemistry and Processing)
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20 pages, 4016 KiB  
Article
Optimization of Green Ultrasound-Assisted Extraction of Carotenoids and Tocopherol from Tomato Waste Using NADESs
by Georgiana Ileana Badea, Florentina Gatea, Simona Carmen Litescu-Filipescu, Andreia Alecu, Ana Chira, Celina Maria Damian and Gabriel Lucian Radu
Molecules 2025, 30(3), 591; https://doi.org/10.3390/molecules30030591 - 28 Jan 2025
Cited by 2 | Viewed by 1626
Abstract
The purpose of this study was to extract the lipophilic fraction from one of the largest source of waste in the industrial sector, namely, the tomato residue from processing the fruit. In order to make this process more environmentally sustainable, this study used [...] Read more.
The purpose of this study was to extract the lipophilic fraction from one of the largest source of waste in the industrial sector, namely, the tomato residue from processing the fruit. In order to make this process more environmentally sustainable, this study used a green extraction protocol employing natural deep eutectic solvents (NADESs) combined with a less energy-consuming technology, the ultrasound-assisted extraction (UAE) method, to simultaneously recover carotenoids and tocopherol from dried powder tomato waste. Two NADESs, one hydrophilic and one hydrophobic, were prepared and compared to support high extraction efficiency and increase the stability of the extracted compounds. The optimal extraction parameters were identified as choline chloride:1,3-butanediol (1:5)-based NADES, a solid-to-liquid ratio of 1:20 (w/v), time of extraction 12 min, temperature 65 °C, radiation frequency 37 Hz, and an ultrasound power level of 70%. The extraction process was intensified and resulted in extracts rich in lycopene (215.13 ± 4.31 μg/g DW), β-carotene (206.95 ± 3.27 μg/g DW), and tocopherol (130.86 ± 8.97 μg/g DW) content, with the highest antioxidant capacity 93.84 ± 0.18 mM Trolox equivalent. Incorporating NADESs for the extraction of bioactive compounds offers numerous benefits, such as improved sustainability, enhanced extraction efficiency, better protection of sensitive compounds, and reduced environmental impact. These advantages make NADESs a promising alternative to traditional organic solvents, especially in industries that require natural, green, and efficient extraction processes for valuable bioactive molecules. Full article
(This article belongs to the Section Green Chemistry)
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19 pages, 1985 KiB  
Article
Valorization of Sour Cherry Kernels: Extraction of Polyphenols Using Natural Deep Eutectic Solvents (NADESs)
by Danica Božović, Ivana Dimić, Nemanja Teslić, Aleksandra Mišan, Milica Pojić, Alena Stupar, Anamarija Mandić, Sanja Milošević, Zoran Zeković and Branimir Pavlić
Molecules 2024, 29(12), 2766; https://doi.org/10.3390/molecules29122766 - 11 Jun 2024
Cited by 4 | Viewed by 1719
Abstract
The objective of this research was to optimize the natural deep eutectic solvent (NADES) extraction process from sour cherry kernels (Prunus cerasus L.). For polyphenol isolation, conventional solid–liquid extraction was employed using different concentrations of ethanol (0, 10, 20, 30, 40, 50, [...] Read more.
The objective of this research was to optimize the natural deep eutectic solvent (NADES) extraction process from sour cherry kernels (Prunus cerasus L.). For polyphenol isolation, conventional solid–liquid extraction was employed using different concentrations of ethanol (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 96%), as well as the innovative NADES extraction technique. In the initial phase of the research, a screening of 10 different NADESs was conducted, while extraction was carried out under constant parameters (50 °C, 1:20 w/w, 60 min). NADES 4, composed of lactic acid and glucose in a molar ratio of 5:1, exhibited the highest efficiency in the polyphenol isolation. In the subsequent phase of the research, response surface methodology (RSM) was utilized to optimize the extraction process. Three independent variables, namely temperature, extraction time, and solid–liquid (S/L) ratio, were examined at three different levels. The extracted samples were analyzed for total phenol (TP) and antioxidant activity using the DPPH, ABTS, and FRAP assays. ANOVA and descriptive statistics (R2 and CV) were performed to fit the applied model. According to RSM, the optimal extraction conditions were determined as follows: temperature of 70 °C, extraction time of 161 min, and S/L ratio of 1:25 w/w. Full article
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15 pages, 2182 KiB  
Article
Combination of Natural Deep Eutectic Solvents and Nano-Liquid Chromatography towards White Analytical Chemistry: A Practical Application
by Álvaro Santana-Mayor, Giovanni D’Orazio, Salvatore Fanali, Miguel Ángel Rodríguez-Delgado and Bárbara Socas-Rodríguez
Separations 2024, 11(4), 119; https://doi.org/10.3390/separations11040119 - 16 Apr 2024
Cited by 3 | Viewed by 2794
Abstract
In this work, a green and practical analytical method based on natural deep eutectic solvents (NADES) as extraction agents and nano-liquid chromatography as a separation technique was developed. To demonstrate the applicability of the methodology, alkylphenols and bisphenol A were evaluated as model [...] Read more.
In this work, a green and practical analytical method based on natural deep eutectic solvents (NADES) as extraction agents and nano-liquid chromatography as a separation technique was developed. To demonstrate the applicability of the methodology, alkylphenols and bisphenol A were evaluated as model compounds in olive and sunflower oils as model fatty samples by liquid–liquid microextraction. With this aim, several NADES based on mixtures of choline chloride with glycerol, lactic, ascorbic, and citric acids or glycerol with amino acids were evaluated as potential extraction solvents. In addition, to select the most suitable stationary phase for the separation of this group of contaminants, some stationary phases were tested, including Pinnacle II phenyl, Cogent Bidentate C18™, and XBridge® C18. The last one provided the best performance with an analysis time of 11 min. To solve the problem of the compatibility of hydrophilic NADES with chromatographic systems without harming the solubility of analytes, different aqueous organic mixtures were tested. Methanol/water mixtures were the most suitable as an injection solvent. Finally, following the White Analytical Chemistry principles, different tools were used to evaluate the greenness, the practicality, and applicability of the method based on the Analytical Eco-Scale, the Analytical GREEnness metric approach, and the Blue Applicability Grade Index. Full article
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18 pages, 1149 KiB  
Review
NaDES Application in Cosmetic and Pharmaceutical Fields: An Overview
by Carla Villa, Debora Caviglia, Francesco Saverio Robustelli della Cuna, Guendalina Zuccari and Eleonora Russo
Gels 2024, 10(2), 107; https://doi.org/10.3390/gels10020107 - 28 Jan 2024
Cited by 30 | Viewed by 8032
Abstract
Natural deep eutectic solvents (NaDES) represent a new generation of green, non-flammable solvents, useful as an efficient alternative to the well-known ionic liquids. They can be easily prepared and exhibit unexpected solubilizing power for lipophilic molecules, although those of a hydrophilic nature are [...] Read more.
Natural deep eutectic solvents (NaDES) represent a new generation of green, non-flammable solvents, useful as an efficient alternative to the well-known ionic liquids. They can be easily prepared and exhibit unexpected solubilizing power for lipophilic molecules, although those of a hydrophilic nature are mostly used. For their unique properties, they can be recommend for different cosmetic and pharmaceutical applications, ranging from sustainable extraction, obtaining ready-to-use ingredients, to the development of biocompatible drug delivery responsive systems. In the biomedical field, NaDES can be used as biopolymer modifiers, acting as delivery compounds also known as “therapeutic deep eutectic systems”, being able to solubilize and stabilize different chemical and galenical formulations. The aim of this review is to give an overview of the current knowledge regarding natural deep eutectic solvents specifically applied in the cosmetic and pharmaceutical fields. The work could help to disclose new opportunities and challenges for their implementation not only as green alternative solvents but also as potential useful pathways to deliver bioactive ingredients in innovative formulations. Full article
(This article belongs to the Special Issue Hydrogel for Sustained Delivery of Therapeutic Agents)
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2 pages, 191 KiB  
Abstract
Reusing Food Waste: Ascorbic Acid Extraction from Orange Peel Using Ultrasound-Assisted Extraction and Natural Deep Eutectic Solvents
by Clara Gomez-Urios, Ines Mbuy, Maria Jose Esteve, Jesus Blesa, Ana Frigola and Daniel Lopez-Malo
Biol. Life Sci. Forum 2022, 18(1), 29; https://doi.org/10.3390/Foods2022-12976 - 30 Sep 2022
Viewed by 1488
Abstract
The food industry generates a huge amount of waste from the production of food and processed products. There is a need to find a different outcome for this waste, use or reuse, to minimize this problem. Regarding citrus fruits, the waste of this [...] Read more.
The food industry generates a huge amount of waste from the production of food and processed products. There is a need to find a different outcome for this waste, use or reuse, to minimize this problem. Regarding citrus fruits, the waste of this cultivar has a significant amount of bioactive compounds, such as ascorbic acid (AA). The extraction of these compounds can also contribute to environmental pollution due to energy usage and polluting organic solvent by-products. Nonconventional extraction techniques and less-polluting solvents to recover these compounds from citrus waste would be a better and less-polluting choice. In this study, six hydrophilic natural deep eutectic solvents (NADESs) were prepared to extract AA from orange peel (navel cultivar). EtOH 50% was used as the control. The extraction was performed with the aid of ultrasound-assisted extraction (UAE). The following optimized UAE parameters were used: extraction time (5, 10, and, 15 min), intensity (100 W, 200 W, and 400 W), and a magnetic stirring time after UAE (0, 20, 30, and 45 min). The determination of AA was made by HPLC-UV/VIS. Mobile phase A included Milli-Q water/formic acid (95:5), while mobile phase B included acetonitrile/A (60:40). An injection volume of 1 µL and a flow rate of 0.5 mL/min were used. A standard calibration curve was constructed using the same conditions as the samples (R = 0.9998). The selected optimal conditions were 10 min of extraction, 100 W of intensity (no statistical differences found among intensities), and 45 min of magnetic stirring after treatment. The NADES that presented the highest extraction yield was malic acid with glucose (11.76 mg/100 mL) followed by L-proline with malic acid (7.44 mg/100 mL). NADEs provided higher extraction yields than did EtOH 50% (5.41 mg/100 mL). In conclusion, two of the studied NADESs extracted more AA from orange peel than did EtOH 50%. Full article
7 pages, 258 KiB  
Proceeding Paper
Assessment of the Use of a Selection of Natural Deep Eutectic Solvents in the Extraction of Polar Bioactive Compounds from Orange Peel
by Alberto Tejero, María Eugenia Martín, Daniel López-Malo, Maria José Esteve, Ana Frigola and Jesús Blesa
Biol. Life Sci. Forum 2021, 6(1), 14; https://doi.org/10.3390/Foods2021-11102 - 14 Oct 2021
Cited by 2 | Viewed by 1526
Abstract
The reuse of food chain residues is topical. This revaluation can extract bioactive compounds from these residues. However, extraction involves chemicals that cause environmental damage. In the present work, an experimental design with natural deep eutectic solvents (NADES) has been carried out for [...] Read more.
The reuse of food chain residues is topical. This revaluation can extract bioactive compounds from these residues. However, extraction involves chemicals that cause environmental damage. In the present work, an experimental design with natural deep eutectic solvents (NADES) has been carried out for extracting bioactive compounds from orange peel residues. NADES have a very low environmental impact. The tests were performed with five different NADES, mixed with 70% water. The results were compared with ethanol–water 50%, v:v, showing that NADES solvents provided better extraction of phenolic compounds and antioxidant capacity. The shelf-life of the extracts was also evaluated, based on the above tests, for 4 weeks, finding significant changes from day 15 of storage at 4 °C. Full article
14 pages, 1271 KiB  
Article
Efficacy of Natural Deep Eutectic Solvents for Extraction of Hydrophilic and Lipophilic Compounds from Fucus vesiculosus
by Ekaterina D. Obluchinskaya, Olga N. Pozharitskaya, Lyubov V. Zakharova, Anna V. Daurtseva, Elena V. Flisyuk and Alexander N. Shikov
Molecules 2021, 26(14), 4198; https://doi.org/10.3390/molecules26144198 - 10 Jul 2021
Cited by 106 | Viewed by 5993
Abstract
The impact of the composition of natural deep eutectic solvents (NADES) and extraction conditions on the simultaneous extraction of hydrophilic ascorbic acid (AA), phlorotannins (TPhC), and lipophilic fucoxanthin (FX) from Fucus vesiculosus was investigated for the first time. In biological tests, the NADES [...] Read more.
The impact of the composition of natural deep eutectic solvents (NADES) and extraction conditions on the simultaneous extraction of hydrophilic ascorbic acid (AA), phlorotannins (TPhC), and lipophilic fucoxanthin (FX) from Fucus vesiculosus was investigated for the first time. In biological tests, the NADES extracts showed the promising ability to scavenge DPPH radicals. A positive correlation was observed between DPPH scavenging activity and AA, TPhC, and FX contents. We calculate the synergistic effect of antioxidants extracted by NADES from F. vesiculosus based on the mixture effect (ME). The addition of 30% water to the NADES and the prolongation of sonication time from 20 min up to 60 min were favorable for the ME. The ME for extracts with the NADES was increased by two folds (ME > 2). In contrast, conventional extraction by maceration with steering at 60 °C does not lead to the synergistic effect (ME = 1). It is notable that the NADES provides high stability and preserves the antioxidant activity of the extracts from F. vesiculosus during storage. Full article
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15 pages, 3090 KiB  
Article
Eco-Friendly 1,3-Dipolar Cycloaddition Reactions on Graphene Quantum Dots in Natural Deep Eutectic Solvent
by Salvatore V. Giofrè, Matteo Tiecco, Consuelo Celesti, Salvatore Patanè, Claudia Triolo, Antonino Gulino, Luca Spitaleri, Silvia Scalese, Mario Scuderi and Daniela Iannazzo
Nanomaterials 2020, 10(12), 2549; https://doi.org/10.3390/nano10122549 - 18 Dec 2020
Cited by 40 | Viewed by 3985
Abstract
Due to their outstanding physicochemical properties, the next generation of the graphene family—graphene quantum dots (GQDs)—are at the cutting edge of nanotechnology development. GQDs generally possess many hydrophilic functionalities which allow their dispersibility in water but, on the other hand, could interfere with [...] Read more.
Due to their outstanding physicochemical properties, the next generation of the graphene family—graphene quantum dots (GQDs)—are at the cutting edge of nanotechnology development. GQDs generally possess many hydrophilic functionalities which allow their dispersibility in water but, on the other hand, could interfere with reactions that are mainly performed in organic solvents, as for cycloaddition reactions. We investigated the 1,3-dipolar cycloaddition (1,3-DCA) reactions of the C-ethoxycarbonyl N-methyl nitrone 1a and the newly synthesized C-diethoxyphosphorylpropilidene N-benzyl nitrone 1b with the surface of GQDs, affording the isoxazolidine cycloadducts isox-GQDs 2a and isox-GQDs 2b. Reactions were performed in mild and eco-friendly conditions, through the use of a natural deep eutectic solvent (NADES), free of chloride or any metal ions in its composition, and formed by the zwitterionic trimethylglycine as the -bond acceptor, and glycolic acid as the hydrogen-bond donor. The results reported in this study have for the first time proved the possibility of performing cycloaddition reactions directly to the p-cloud of the GQDs surface. The use of DES for the cycloaddition reactions on GQDs, other than to improve the solubility of reactants, has been shown to bring additional advantages because of the great affinity of these green solvents with aromatic systems. Full article
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11 pages, 1616 KiB  
Article
Natural Deep Eutectic Solvent Extraction of Flavonoids of Scutellaria baicalensis as a Replacement for Conventional Organic Solvents
by Wim Wouter Oomen, Paloma Begines, Natali Rianika Mustafa, Erica G. Wilson, Robert Verpoorte and Young Hae Choi
Molecules 2020, 25(3), 617; https://doi.org/10.3390/molecules25030617 - 31 Jan 2020
Cited by 106 | Viewed by 8142
Abstract
Natural deep eutectic solvents (NADES) are a type of ionic liquid (IL) or deep eutectic solvent (DES), the ingredients of which are exclusively natural products (non-toxic and environmentally friendly). Here, we explore the potential of NADES as an alternative to conventional organic solvents [...] Read more.
Natural deep eutectic solvents (NADES) are a type of ionic liquid (IL) or deep eutectic solvent (DES), the ingredients of which are exclusively natural products (non-toxic and environmentally friendly). Here, we explore the potential of NADES as an alternative to conventional organic solvents (e.g., aqueous methanol or ethanol) for the extraction of flavonoids from Scutellaria baicalensis stem bark to investigate their extractability depending on structural variation. Four NADES, each containing citric acid in combination with β-alanine, glucose, xylitol, or proline (at a molar ratio of 1:1), and a variable amount of water, were used to extract the flavonoid aglycones: baicalein (1), scutellarein (3), wogonin (5), and oroxylin A (7), and their glycosides, baicalin (2), scutellarin (4), wogonoside (6) and oroxyloside (8) from the powdered bark of S. baicalensis. The chemical profile and yield of the extracts were determined using HPTLC and HPLC. The extractability of individual flavonoids was found to be influenced by the concentration of water (20–60%, w/w) in the NADES. Among the tested flavonoids, the extraction yield of baicalein (1), scutellarein (3), wogonin (5), oroxylin A (7) with NADES was 2 to 6 times that of aqueous methanol. However, the amount of their corresponding glycosides (baicalin (2), wogonoside (6) and oroxyloside (8)) extracted with NADES was only 1.5–1.8 times higher than with aqueous methanol. Interestingly, the more hydrophilic glycosides were less extracted than their corresponding aglycones despite the high hydrophilicity of the NADES. These results prove that NADES may be used for extraction of compounds with a wide range of hydrophilicity. Full article
(This article belongs to the Collection Preanalytical Methods for Natural Products Production)
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10 pages, 2494 KiB  
Article
Green and Efficient Ultrasonic-Assisted Extraction of Bioactive Components from Salvia miltiorrhiza by Natural Deep Eutectic Solvents
by Xinping He, Jiehong Yang, Yan Huang, Yin Zhang, Haitong Wan and Chang Li
Molecules 2020, 25(1), 140; https://doi.org/10.3390/molecules25010140 - 29 Dec 2019
Cited by 53 | Viewed by 4984
Abstract
Natural deep eutectic solvents (NaDESs) are recently developed green solvent alternatives to conventional fossil solvents. The present work systematically screened 22 different NaDESs for the ultrasonic-assisted extraction of bioactive components from Salvia miltiorrhiza (SM), a widely used traditional Chinese medical plant. The suitable [...] Read more.
Natural deep eutectic solvents (NaDESs) are recently developed green solvent alternatives to conventional fossil solvents. The present work systematically screened 22 different NaDESs for the ultrasonic-assisted extraction of bioactive components from Salvia miltiorrhiza (SM), a widely used traditional Chinese medical plant. The suitable solvent and extraction condition were optimized in a two-round screening. In comparison with fossil solvents, NaDESs, especially L-proline-lactic acid (L-Pro-Lac) showed significant advantages in the extraction of salvianolic acid B (SAB), tanshinone IIA (TIIA) and cryptotanshinone (CYT). The optimized yields of the three targeting compounds were 42.05, 1.485 and 0.839 mg/g, respectively. The present method was also applied to the pretreatment of SM samples from different geographic origins. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities of NaDES extracts were determined in the study to prove the feasibility of NaDES in bioactive component extraction. The application of NaDESs in the extraction of both hydrophilic and hydrophobic small molecules from SM is proved to be a green and efficient method for pretreatment of herbal materials. Full article
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