Natural deep eutectic solvents occupy a curious place in chemistry. They arise when certain natural compounds, typically a hydrogen bond donor and a hydrogen bond acceptor such as an amino acid, a sugar, an organic acid or choline chloride, are mixed in specific ratios. The resulting mixture behaves in a striking way: instead of crystallizing as its individual components would, it melts or remains liquid at temperatures far lower than either ingredient alone, forming a stable eutectic liquid. The concept gained prominence in 2011, when researchers proposed in Plant Physiology that such mixtures might be the missing link in understanding cellular metabolism, since cells are crowded with exactly these kinds of small molecules. By 2013, Dai and colleagues had framed NADES as a new potential medium for green technology, and the field has expanded steadily since.

What makes NADES attractive to pharmaceutical scientists is the combination of properties they bring to the table. They are largely non-toxic, biodegradable and inexpensive to produce, often from food-grade or metabolite-grade starting materials. They can be synthesized sustainably by several methods, and their characteristics can be tuned, for example by adjusting water content, which alters viscosity and other physicochemical parameters. Studies have shown that adding water tailors NADES properties to facilitate applications, and that these solvents even modulate the thermal behavior of water, which has led to their exploration as non-toxic cryoprotective agents. Crucially for drug delivery, NADES excel at dissolving poorly water-soluble molecules, a chronic bottleneck, since a large fraction of active pharmaceutical ingredients and phytochemicals exhibit solubility so low that oral absorption becomes unreliable.

The review’s central argument is that pairing NADES with nanocarriers multiplies these advantages. Conventional drug delivery systems face a familiar litany of shortcomings: lack of targeted delivery, fluctuation in drug release, possible side effects, frequent dosing requirements, environmental hazards and high costs. Nanocarrier-based delivery already offers substantial rewards over conventional systems, but the carriers themselves often rely on solvents and excipients that raise toxicity or environmental concerns. The authors highlight, for instance, pro-inflammatory concerns that have been raised with lipid nanoparticles, the platform behind mRNA vaccines, and safety questions surrounding these systems for nucleic acid delivery. NADES-integrated nanocarriers, by contrast, promise low toxicity, biodegradability, cost-effectiveness and tunability, while enhancing the therapeutic efficacy of bioactive drugs.

The technical landscape covered in the review is broad. Solid lipid nanoparticles and nanostructured lipid carriers, established platforms for improving bioavailability and enabling targeted therapy, have been combined with NADES to encapsulate compounds such as curcumin, a notoriously insoluble but biologically active polyphenol. One 2024 study reported enhanced curcumin delivery and stability through NADES-based niosomes, vesicular carriers assembled from non-ionic surfactants. Another line of work integrated natural deep eutectic solvents into nanostructured lipid carriers with an explicitly industrial outlook, and a 2025 study used green nanostructured lipid carriers and NADES to solubilize extracts from Brazilian Cerrado byproducts, boosting antioxidant potential and simultaneously valorizing agricultural waste. Thermosensitive niosomes have even been designed from eutectic mixtures of natural fatty acids, adding stimulus-responsive behavior to the toolkit.

Polymeric systems feature prominently as well. Researchers have synthesized biodegradable poly(2-hydroxyethyl methacrylate) using NADES for sustainable cancer drug delivery, and fabricated green poly(vinyl alcohol) nanofibers with NADES for fast-dissolving drug delivery. Doxorubicin, a mainstay chemotherapy agent, has been loaded onto functional graphene nanocarriers using ternary deep eutectic solvent systems. A targeted solid-liquid polymer carrier supported by NADES has been explored for breast cancer therapy. Beyond polymers, the review describes NADES-based surfactant-free microemulsions that solubilize and extract curcumin from turmeric, and eutectogels, gel networks formed within deep eutectic solvents, that have been engineered for colon-targeted delivery of mesalazine, an anti-inflammatory drug used in inflammatory bowel disease. Smart supramolecular eutectogels have been designed for pH- and thermo-responsive transdermal delivery of anticancer curcumin, illustrating how the platform can incorporate environmental triggers.

The application domains extend well beyond cancer. In wound care, a curcumin emulgel enriched with a camphor-menthol-based deep eutectic solvent demonstrated wound healing efficacy, and NADES-based chitosan hydrogels have been developed for enhanced photoimmunomodulation treatment of various wounds. Nano-electrospun membranes combining NADES with Platostoma palustre polysaccharides and polyvinyl alcohol showed transdermal properties and bioactivity. In dermatology, a deep eutectic solvent-assisted kaempferol hydrogel emerged as a promising therapeutic approach for psoriasis-like skin inflammation. Ocular medicine has joined in too: green-sourced polyphenols delivered through a sustainable NADES-based approach have been proposed for dry eye disease treatment. Cosmeceutical applications include the green extraction of Rosa canina and Prunus spinosa by NADES followed by encapsulation in chitosan nanoparticles, and deep eutectic solvent nanoparticles have been used to enhance intradermal delivery of hyaluronic acid for anti-aging and moisturizing effects.

The mechanisms underlying these systems are as varied as the formulations. NADES can act as solubilizing media within the carrier, as structural components of the carrier itself, or as permeation enhancers that interact with biological membranes. Research into how NADES interact with artificial and natural membranes supports their role in facilitating transport across the skin and mucosal barriers. Choline chloride-malic acid NADES containing hydrophobic drugs has been studied for solubility and permeability behavior in digestive tract models, informing oral delivery design. Methotrexate solubilization and transdermal delivery have been enhanced in microemulsions with NADES screened by computational COSMO-RS methods, showing how molecular simulation can guide solvent selection. Pharmacokinetic evidence is accumulating as well: rutin dissolved in a proline-glycine NADES showed improved bioavailability after oral administration in rats, and deep eutectic solvents altered the pharmacokinetics of salvianolic acid B in rats, with acute toxicity testing performed alongside. Notably, NADES have also been shown to protect RNA from thermal degradation, and a ready-to-use lipid nanoparticle technology for nucleic acid delivery based on deep eutectic solvents has been developed, hinting at relevance for gene therapy and mRNA medicine.

Safety data, while still maturing, are encouraging. Cytotoxicity profiling of choline chloride-based NADES has been carried out, and toxicity studies of a betaine-glycerol NADES in rats have been published. A noncytotoxic, hemocompatible ion gel was prepared by self-polymerization of 2-hydroxyethyl methacrylate in a green deep eutectic solvent, and hydrogel formulations containing lidocaine have incorporated NADES to advantage. Buccal xanthan gum-hyaluronic acid eutectogels with dual anti-inflammatory and antimicrobial properties have been reported, relevant given the well-documented organ damage and gastrointestinal risks associated with long-term nonsteroidal anti-inflammatory drug use. Alginate hydrogels incorporating essential oils loaded in chitosan nanoparticles extend the platform to biomedical applications such as antimicrobial wound management.

The review is candid about the obstacles standing between laboratory promise and clinical reality. Viscosity, limited recyclability and safety data, long-term stability and scalability remain key issues for large-scale industrial application. High viscosity complicates handling, mixing and manufacturing; the recyclability of these solvents at industrial scale is not yet established; and comprehensive long-term safety and stability profiles are still being assembled. Regulatory pathways for such novel combination products also require clarification, a theme echoed in broader discussions of nanopharmaceutical quality-by-design frameworks and post-marketing surveillance. The authors frame their work as identifying these challenges, research gaps and opportunities for translating NADES-based nanocarrier technologies from laboratory scale to clinical and industrial application, and as a theoretical foundation for broader use in pharmaceutical and biomedical fields. If those gaps close, the vision is compelling: drug carriers built from the same molecular vocabulary that cells themselves use, delivering difficult medicines more safely, more sustainably and more effectively.

Subject of Research: Natural deep eutectic solvent-based nanocarriers for sustainable drug delivery

Article Title: Engineering green nanocarriers using natural deep eutectic solvents: a sustainable platform for modern drug delivery

Article References: Patil, N. B., & Gopinath, S. C. B. (2026). Engineering green nanocarriers using natural deep eutectic solvents: a sustainable platform for modern drug delivery. Journal of Nanoparticle Research, 28(9), Article 233. https://doi.org/10.1007/s11051-026-06749-0

Image Credits: AI Generated

DOI: 10.1007/s11051-026-06749-0

Keywords: natural deep eutectic solvents, NADES, nanocarriers, drug delivery, green chemistry, lipid nanoparticles, niosomes, eutectogels, curcumin, biomedicine, pharmaceuticals, sustainability

The stakes are considerable. Lutein is the second most valuable carotenoid produced from microalgae after astaxanthin, feeding a global market currently worth about 309 million US dollars and projected to reach 406 million by 2026. Beyond supplements and food additives, the pigment’s potent antioxidant activity has made it a fixture of research into human eye health. Traditional extraction, however, leans on solvents such as tetrahydrofuran, acetone, and diethyl ether, all of which are flammable, volatile, and raise toxicity concerns. Supercritical carbon dioxide offers an alternative but demands heavy energy inputs, while ionic liquids, though effective, are costly to synthesize and not readily biodegradable, hampering their scale-up.

NADESs occupy a sweet spot between performance and sustainability. These solvents form when a hydrogen bond acceptor, such as the plant-derived compound thymol, is mixed with a hydrogen bond donor, such as decanoic acid or isoborneol, and gently heated. The components melt together into a liquid whose hydrogen bonding network gives it unusual solvation powers. Unlike conventional solvents, they require no purification step, generate no synthetic waste, and break down readily in the environment. Crucially for carotenoid work, many NADESs also suppress oxidative degradation, meaning the pigment they extract tends to survive longer.

In the new study, the researchers synthesized six different NADES formulations and characterized them thoroughly using infrared spectroscopy, viscometry, and density measurements. The telltale signature of successful eutectic formation appeared in the spectra: the hydroxyl stretching band of thymol shifted from roughly 3175 to 3418 inverse centimeters, and the carbonyl band of decanoic acid moved to higher wavenumbers, confirming that hydrogen bonds had stitched the components into a new liquid. Densities fell between 0.90 and 0.94 grams per cubic centimeter, while viscosities spanned a wide range, from a pourable 11.67 to a sluggish 98.40 millipascal-seconds at room temperature, a property the team knew would matter enormously for mass transfer during extraction.

The real innovation, however, came before any solvent touched the algae. Chlorella cells are wrapped in tough cell walls that resist solvent penetration, so the team pretreated the biomass in a planetary ball mill, essentially a jar of grinding beads that pulverizes the cells through high-speed collisions. Optimizing three variables proved decisive. Milling for 30 minutes at 400 revolutions per minute with a biomass-to-beads ratio of 1:30 lifted the lutein yield from 0.61 to 2.02 milligrams per gram of dry biomass. Pushing the speed to 500 rpm actually backfired: centrifugal forces compacted the biomass into a cake layer on the jar walls and balls, wasting energy and partially degrading the pigment. Scanning electron microscopy revealed the physical aftermath, with pretreated cells visibly ruptured and shrunken, and surface area measurements confirmed the effect, rising from 4.13 to 7.30 square meters per gram after milling.

When the milled biomass met the solvent candidates, one formulation stood out. A 1:1 mixture of thymol and isoborneol, designated N3, outperformed all five competitors and beat the conventional solvent ethyl acetate, which yielded only 1.62 milligrams per gram. The researchers note that these particular thymol and menthol-based eutectic mixtures had never previously been applied to lutein recovery from microalgae. The chemistry of the extracts told its own story: acid-containing NADESs produced yellowish extracts as acidic conditions converted chlorophylls into pheophytins, stripping magnesium from the porphyrin ring, while the non-acidic N3 yielded the green tinge characteristic of intact chlorophyll co-extraction.

Fine-tuning the extraction itself pushed yields higher still. A solid-to-liquid ratio of 0.067 grams per milliliter proved optimal, delivering 33.86 percent more lutein than a leaner ratio, while diluting the NADES with ethanol to a 50:50 blend cut viscosity dramatically, from the neat solvent down to under 2 millipascal-seconds in some dilutions, and boosted recovery to 2.34 milligrams per gram. A single extraction cycle sufficed to capture most of the pigment, a direct payoff of the ball milling pretreatment, though additional cycles squeezed out further gains.

Perhaps the most forward-looking result concerns solvent recycling, a persistent headache for eutectic solvent chemistry because the strong molecular interactions that make NADESs good extractants also make them hard to separate from the extracted compounds. Using a graphitized carbon black cartridge in a solid-phase extraction setup, the team demonstrated that the NADES-ethanol blend retained 88.40 percent of its original extraction efficiency after one recycling cycle, 82.46 percent after two, and still a workable 70.89 percent after three. The trapped lutein itself could be eluted from the cartridge with 2-methyltetrahydrofuran, recovered at 56.41 percent efficiency, meaning neither the pigment nor the solvent is simply thrown away.

The NADES system also proved a better bodyguard for the delicate pigment. Lutein degrades under heat, light, and oxygen, and isomerizes into less useful forms when overheated. In thermal challenge tests at 40, 60, and 80 degrees Celsius, lutein dissolved in the NADES-ethanol blend degraded just 2.53 percent in the first half hour at 40 degrees, compared with 7.05 percent in methanol, and after 150 minutes the NADES sample still held 85.1 percent of its lutein versus 81.02 percent for the methanol control. Half-life calculations underscored the difference: 608 minutes at 40 degrees Celsius in the NADES blend against 450 minutes in methanol. Thermodynamic analysis showed the degradation required more activation energy in the NADES system, 18.73 versus 11.79 kilojoules per mole, meaning the solvent imposes a higher energy barrier against breakdown, and positive Gibbs free energy values confirmed the pigment does not degrade spontaneously in either medium.

A formal sustainability audit sealed the comparison. Using the Green Analytical Procedure Index, which scores every stage of a method from reagents to waste disposal with color-coded pictograms, the NADES-based process earned six green, seven yellow, and two red ratings, while a traditional organic solvent extraction scored three green, eight yellow, and four red. The gap stemmed chiefly from safer extractants and recyclable solvent handling. Taken together, the findings sketch a pipeline in which rapidly grown, carbon-sequestering microalgae are shattered by precisely tuned mechanical forces, their lutein dissolved in plant-derived liquids that can be reused repeatedly, and the pigment protected all the way to the bottle. For a market hungry for natural antioxidants, that combination of efficiency, mildness, and green credentials may be exactly what sustainable carotenoid production has been waiting for.

Subject of Research: Sustainable extraction of the carotenoid lutein from microalgae using ball milling and natural deep eutectic solvents

Article Title: Efficient ball milling assisted approach to recover lutein from microalgae biomass with natural deep eutectic solvents

Article References: Muhammad, G., Yuan, X., Li, Z., Zhang, X., & Zhang, Z. (2026). Efficient ball milling assisted approach to recover lutein from microalgae biomass with natural deep eutectic solvents. Results in Chemistry, 30, Article 103861. https://doi.org/10.1016/j.rechem.2026.103861

Image Credits: AI Generated

DOI: 10.1016/j.rechem.2026.103861

Keywords: lutein, microalgae, Chlorella pyrenoidosa, natural deep eutectic solvents, ball milling, green extraction, carotenoids, antioxidants, solvent recycling, thermal stability, biorefinery, sustainability

Natural deep eutectic solvents, or NaDES, have emerged in recent years as one of the most promising tools in green chemistry. These liquids are formed when certain natural compounds, such as sugars, alcohols, and organic acids, are mixed together in specific ratios, causing them to melt into a stable liquid through an extensive network of hydrogen bonds. Unlike many conventional organic solvents, NaDES are typically non-toxic, biodegradable, inexpensive, and tunable in polarity, which makes them attractive replacements for the volatile organic solvents that have long dominated phytochemical extraction. The United Nations has explicitly called for a transition away from traditional organic solvents as part of its 2030 Agenda for Sustainable Development, and NaDES chemistry is one of the leading answers to that call.

The research team selected two contrasting NaDES for their investigation. The first was a hydrophilic mixture of glycerol and choline chloride, abbreviated GCC, prepared by heating the two components in a one-to-three molar ratio at 70 degrees Celsius until a clear viscous liquid formed. The second was a hydrophobic blend of camphor and thymol, abbreviated CT, which liquefied within ten minutes at 35 to 40 degrees Celsius in a one-to-one ratio. Because deep eutectic solvents are inherently viscous and struggle to penetrate plant tissue on their own, the researchers diluted the GCC system with water and the CT system with acetonitrile, lowering viscosity and improving the solvents’ ability to reach the phytochemicals locked inside the leaf matrix.

To squeeze the maximum performance out of each solvent system, the team turned to microwave-assisted extraction, a technique that heats the solvent and plant material from the inside out. Microwaves interact with polar molecules by inducing dipole rotation, generating heat directly within the extraction medium. This localized heating builds internal pressure inside plant cells, rupturing cell walls and releasing intracellular compounds far faster than conventional stirring or reflux methods. The approach conserves energy, slashes extraction times to mere seconds, and reduces the risk of degrading heat-sensitive molecules because the total exposure window is so short. In this study, powdered leaves were combined with 30 milliliters of the solvent-diluent mixture in a conical flask and irradiated in a domestic microwave oven at controlled power and duration settings.

Optimizing the process required a statistical framework capable of mapping how multiple variables interact simultaneously. The researchers employed response surface methodology using a Box-Behnken design, which generated 17 experimental runs per solvent system with five replicates at central points. Three factors were varied across three levels each: the concentration of the NaDES in its diluent, the microwave power ranging from 220 to 440 watts, and the irradiation time ranging from 20 to 40 seconds. Five responses were measured for every run: total phenolic content expressed as gallic acid equivalents, total flavonoid content expressed as rutin equivalents, DPPH radical scavenging activity expressed as ascorbic acid equivalents, ABTS radical cation scavenging activity expressed as Trolox equivalents, and metal iron chelating activity expressed as EDTA equivalents, all normalized to grams of dry leaf powder.

The results exposed a striking polarity-driven divide between the two solvent systems. The hydrophilic GCC system proved dramatically superior for phenolic recovery, achieving a predicted optimal total phenolic content of 137.49 milligrams of gallic acid equivalents per gram of dry weight, nearly three times the 48.35 milligrams obtained with the hydrophobic CT system. The GCC extracts also dominated in ABTS radical scavenging, reaching 11.57 milligrams of Trolox equivalents per gram, while the CT extracts managed only 0.17 milligrams. This makes chemical sense: the ABTS assay operates through single-electron transfer and preferentially detects highly polar antioxidant molecules, which dissolve readily in the hydrogen-bonding, water-compatible environment that glycerol and choline chloride provide.

The story reversed for flavonoids. The hydrophobic camphor-thymol system extracted 61.72 milligrams of rutin equivalents per gram, roughly five times the 12.17 milligrams achieved by GCC. Many flavonoids possess substantial hydrophobic aromatic ring systems, and the non-polar character of camphor and thymol enables favorable hydrophobic and pi-pi interactions with these structures. The CT system also edged out GCC slightly in DPPH radical scavenging, at 28.38 versus 27.08 milligrams of ascorbic acid equivalents per gram, and in metal chelating activity, at 23.39 versus 21.38 milligrams of EDTA equivalents per gram, suggesting that a meaningful fraction of the leaf’s lipophilic antioxidants and metal-binding ligands are better captured in the hydrophobic medium. Both systems produced comparable DPPH responses overall, indicating that radical-scavenging compounds were extracted efficiently across most processing conditions.

The statistical models underlying these findings proved highly reliable, with coefficients of determination exceeding 0.91 for every response and non-significant lack-of-fit tests confirming that the quadratic equations adequately described the experimental data. Solvent concentration emerged as the most influential variable, followed by microwave power and extraction time. For the GCC system, moderate DES concentration around 75 percent paired with 220 watts and 40 seconds produced optimal results with a desirability value of 1.0, and experimental validation showed relative standard deviations between 0.15 and 5.10 percent. For the CT system, the optimum landed at 60 percent DES concentration in acetonitrile, 220 watts, and 30 seconds, with validation deviations between 0.16 and 6.25 percent. The researchers explain that too much water in the GCC mixture dilutes its solubilizing power for moderately polar polyphenols, while too little water leaves the solvent too viscous to penetrate the biomass, so an intermediate composition balances fluidity and polarity. Similarly, acetonitrile lowers the viscosity of the hydrophobic CT solvent while adding just enough polarity to assist extraction.

Beyond simple solubility, the study highlights a deeper mechanism by which NaDES enhance recovery: direct attack on the plant cell wall. The chloride ions of the GCC mixture can form hydrogen bonds with the hydroxyl groups of cellulose, disrupting the wall’s architecture, while camphor and thymol interact with cell wall components in their own way. Combined with the internal pressure buildup from microwave dielectric heating, this dual assault on cellular structure accelerates the desorption and release of target compounds from the plant matrix. The authors conclude that microwave-assisted extraction coupled with carefully chosen NaDES offers a sustainable, rapid, and selective strategy for recovering antioxidant phytochemicals from Eucalyptus citriodora leaves, and that the choice between hydrophilic and hydrophobic solvents should be guided by the specific class of biomolecules a manufacturer or researcher wishes to target, whether for nutraceutical, pharmaceutical, or food applications.

Subject of Research: Microwave-assisted extraction of phenolic and antioxidant compounds from Eucalyptus citriodora leaves using hydrophilic and hydrophobic natural deep eutectic solvents

Article Title: Microwave-assisted extraction of phenolic and antioxidant compounds from Eucalyptus citriodora leaves using hydrophilic and hydrophobic natural deep eutectic solvents

Article References: Asif, M., & Ahmed, D. (2026). Microwave-assisted extraction of phenolic and antioxidant compounds from Eucalyptus citriodora leaves using hydrophilic and hydrophobic natural deep eutectic solvents. Discover Green Chemistry, 1(1), Article 21. https://doi.org/10.1007/s44509-026-00025-z

Image Credits: AI Generated

DOI: 10.1007/s44509-026-00025-z

Keywords: Eucalyptus citriodora, natural deep eutectic solvents, microwave-assisted extraction, green chemistry, polyphenols, flavonoids, antioxidant activity, response surface methodology, glycerol-choline chloride, camphor-thymol, DPPH, ABTS

Cassia absus belongs to the Fabaceae family and grows in tropical and subtropical regions of Asia. Its seeds have a history of medicinal use and contain reported bioactive constituents including chaksine and isochaksine. That traditional and phytochemical background made the plant a candidate for a more systematic investigation of its extractable compounds. The researchers were not testing a finished medicine or demonstrating a treatment for disease; they were developing and optimizing a laboratory extraction process. The distinction matters because measurements such as antioxidant activity in a test tube do not establish clinical benefit. They do, however, help characterize extracts and identify whether a plant material may warrant further chemical, toxicological and pharmaceutical study.

The process began with seeds purchased from a local market in Lahore, Pakistan. The seeds were washed, dried, ground and passed through an 80-mesh sieve to produce a relatively uniform powder. The material was defatted by soaking it in n-hexane for three days, then dried at 40 degrees Celsius. For the greener extraction stage, the researchers prepared the deep eutectic solvent by combining choline chloride and glycerol in a 1:3 molar ratio. The mixture was heated at 80 degrees Celsius for two hours under vacuum until it formed a clear, colourless liquid. For extraction, the solvent was mixed with water in equal proportions. This water-containing system was then brought into contact with one gram of the prepared seed powder.

Ultrasound supplied the physical force intended to open the plant matrix. When a probe emits high-intensity sound into a liquid, microscopic bubbles can form, grow and collapse in a phenomenon known as acoustic cavitation. These rapid events can disturb cell walls, improve wetting and solvent penetration, and increase movement of dissolved molecules from the solid material into the surrounding liquid. The technique can therefore accelerate mass transfer compared with passive soaking. But more energy or more time is not automatically better. Excessive sonication can increase heating, alter fragile compounds or reduce the energy delivered efficiently through the liquid. The researchers monitored temperature and avoided excessive heat build-up while varying ultrasound amplitude, extraction time and solvent-to-feed ratio across a Box–Behnken experimental design.

The study evaluated four responses: total phenolic content, total flavonoid content, DPPH radical-scavenging activity and iron-chelating activity. Total phenolic content was expressed as milligrams of gallic acid equivalents per gram, while flavonoid content was reported using a rutin-equivalent calibration. DPPH testing measures how effectively an extract reduces a stable laboratory radical, producing an estimate of radical-scavenging capacity. The iron-chelation assay examined the ability of the extract to interfere with the reaction between ferrous ions and ferrozine, with lower colour formation corresponding to greater apparent chelation. These are widely used screening measurements, but they represent chemical behaviour under defined assay conditions rather than proof that the extract will neutralize radicals or regulate iron in a human body.

Seventeen experimental runs, including five centre points, were used to map how the three process variables affected the four responses. The results showed that no single run maximized every measurement. One run produced the highest total phenolic content at 44.18 milligrams of gallic acid equivalents per gram, another produced the highest flavonoid content at 29.26 milligrams of rutin equivalents per gram, a third reached 89.53 percent DPPH radical-scavenging activity, and a fourth recorded 90.31 percent iron-chelating activity. This divergence reflects the chemical complexity of extraction. Phenolics, flavonoids and other active constituents differ in polarity, solubility and stability, so conditions that release one group efficiently may not recover another group or preserve its activity. Maximizing one result could consequently produce an extract that performs poorly across the broader set of desired properties.

Response surface methodology was used first to fit second-order polynomial models describing linear, quadratic and interaction effects. The models were statistically significant for all four responses, with p-values below 0.0001 for phenolic and flavonoid content, 0.0011 for DPPH activity and 0.0024 for iron-chelating activity. Model R-squared values ranged from 0.9299 to 0.9933, indicating that the equations accounted for much of the variation within the tested design space. The solvent-to-feed ratio emerged as the strongest influence on phenolic and flavonoid recovery. Increasing solvent availability likely improved penetration and maintained a concentration gradient that favoured diffusion, but the negative quadratic terms showed that the benefit eventually levelled off or declined. Too much solvent could dilute the extract or reduce ultrasonic energy density.

The antioxidant response was more complicated. Extraction time had a significant negative effect on DPPH activity, suggesting that prolonged sonication may have degraded or structurally modified sensitive radical-scavenging compounds. Ultrasound amplitude and solvent-to-feed ratio also interacted, meaning their effects could not be interpreted independently. Iron-chelating activity was governed mainly by quadratic effects rather than simple increases or decreases in individual variables. The researchers then trained a feedforward artificial neural network using 70 percent of the experimental data for training, with 15 percent each reserved for validation and testing. The selected network used two hidden layers containing 20 and 10 neurons, with logsig and tansig activation functions. Its overall correlation values ranged from 0.97256 for iron-chelating activity to 0.99469 for total phenolic content, although the small dataset means these strong figures apply only within the investigated range and require confirmation with additional experiments.

TOPSIS provided the final decision framework by treating every experimental run as an alternative and all four responses as beneficial criteria. The data were normalized, given equal weights and compared with an ideal solution representing the best combined performance. Run 12 achieved the highest closeness coefficient, 0.7153, at 60 percent amplitude, six minutes and 20 millilitres per gram. Its measured results were 33.51 milligrams of gallic acid equivalents per gram of total phenolics, 27.99 milligrams of rutin equivalents per gram of flavonoids, 74.70 percent DPPH activity and 82.33 percent iron-chelating activity. It did not lead every individual category, but it offered the strongest overall balance. Compared with the lowest-ranked run, it had approximately 2.7 times more total phenolics, 27 percent higher flavonoid content and 59 percent higher DPPH activity, despite slightly lower iron-chelating activity.

The modelling comparison gave the neural network a modest advantage over response surface methodology. At the selected condition, the artificial neural network showed prediction errors of 1.15 percent for flavonoid content and 2.18 percent for DPPH activity, while TOPSIS was closest for total phenolic content with a 1.03 percent error. All models predicted iron-chelating activity with errors below 1 percent. Across the dataset, the neural network generally produced lower average absolute deviations and mean absolute percentage errors, particularly for the nonlinear antioxidant and chelation responses. The researchers also assessed the method with the ComplexMoGAPI green analytical metric, which gave an overall score of 81. The favourable score reflected the use of a choline chloride–glycerol and water system, room-temperature extraction, short sonication and avoidance of more hazardous conventional solvents. However, the reported E-factor was 60, and extraction yield remained below 70 percent, showing that waste and solvent efficiency still need improvement.

The findings position the method as a promising laboratory framework rather than an industrially validated product. Natural deep eutectic solvents can be tuned by changing their components and proportions, and their low volatility and biodegradability are attractive for natural-product processing. Yet solvent recovery, viscosity, long-term stability, compound identification and scale-up must be addressed before commercial adoption. The researchers recommend compound-level characterization, stability testing, toxicity evaluation and pilot-scale validation. Future work could also examine whether the solvent can be reused, whether lower solvent volumes can maintain performance and which specific molecules account for the measured activities. For now, the study demonstrates how acoustic cavitation and data-driven optimization can turn a traditional plant resource into a more systematically studied extraction target, while also showing that a greener label does not eliminate the need to measure waste, validate predictions and test biological claims carefully.

An important consideration is that the reported response values are operational measurements tied to the extraction and assay protocols. Total phenolic and flavonoid results depend on the calibration standards used, while DPPH and iron-chelation values summarize reactions in controlled chemical systems. They can therefore be useful for comparing extraction conditions without identifying which individual seed constituents produced the response. Chemical profiling would be needed to connect the optimized process with specific molecules such as the reported Cassia absus alkaloids or other extract components.

The optimization also illustrates why process conditions should be treated as a defined operating window rather than a universal recipe. The selected settings were derived from a Box–Behnken design covering particular amplitude, time and solvent-to-feed ranges, with a 50:50 NaDES–water extraction mixture and pretreated seed powder. Performance outside those conditions cannot be inferred from the model alone. Changes in particle characteristics, solvent composition, equipment geometry or temperature control could alter cavitation and mass transfer. Independent confirmation using new batches of seeds, expanded chemical characterization and scale-relevant equipment would help establish how reproducible the balance identified by TOPSIS is.

Subject of Research: AI-guided ultrasound extraction of Cassia absus seed phytochemicals using a natural deep eutectic solvent

Article Title: Artificial neural network and TOPSIS guided ultrasound extraction of Cassia absus L. seed phytochemicals using a natural deep eutectic solvent

Article References: Khalid, N. U. A., Iftikhar, H., Ahmed, D., & Mushtaq, M. (2026). Artificial neural network and TOPSIS guided ultrasound extraction of Cassia absus L. seed phytochemicals using a natural deep eutectic solvent. Discover Green Chemistry, 1(1), Article 26. https://doi.org/10.1007/s44509-026-00031-1

Image Credits: AI Generated

DOI: 10.1007/s44509-026-00031-1

Keywords: Cassia absus, green extraction, natural deep eutectic solvents, ultrasound extraction, artificial neural networks, TOPSIS, antioxidants, phytochemicals, Artificial, neural, network, guided

Lignin plays a crucial role in the structural integrity of plants, providing strength and resistance against microbial attack. However, its recalcitrance complicates the process of converting biomass into biofuels and other valuable chemicals. Traditional methods such as hydrothermal treatment, while effective in breaking down plant cell walls to release sugars, inadvertently lead to the degradation of lignin. This dual loss—one due to the energy-intensive hydrothermal process and the other from the resultant degradation of lignin—has long plagued researchers in the field.

The new approach introduced by Raj and Singh employs natural deep eutectic solvents (NADES), a type of salt solution that offers a gentler alternative for breaking down lignin’s complex structures. Unlike hydrothermal methods that rely on high temperatures and pressures, NADES operate effectively at room temperature, significantly reducing energy costs and environmental impact. This technique not only preserves the native structure of lignin but also enhances the yields of cellulose and sugars, essential precursors for biofuel production.

One of the key advantages of using NADES lies in their ability to maintain the integrity of lignin during extraction. Raj and his team demonstrated that by using carefully selected combinations of these natural solvents, they could separate lignin from cellulose and hemicellulose without causing it to condense into an impenetrable mass, a common occurrence with hydrothermal methods. The ability to retain lignin’s native structure unlocks its potential for further chemical transformations, creating a pathway for a multitude of bioproducts.

The implications of this research reach far beyond just biofuels. As the global demand for renewable energy sources increases, efficient and sustainable conversion processes become essential. The lignin extracted using this novel method is not only more accessible for further chemical conversion but also maintains its properties, allowing it to be used in producing aromatic compounds and oils. Such versatility opens up new avenues for creating high-value bioproducts, positioning lignin as a vital resource in the burgeoning bioeconomy.

Moreover, the economic feasibility of the NADES pretreatment method is noteworthy. The operational costs are significantly lower than conventional hydrothermal processes, and the solvents used can be recycled multiple times without losing their effectiveness. This recycling capability not only reduces waste but also enhances the sustainability of the process, making it an attractive option for commercial biofuel production facilities.

In addition to its operational advantages, the NADES method is described as “feedstock agnostic.” This means that it can be applied to a wide array of biomass sources, ranging from agricultural residues to dedicated bioenergy crops like Miscanthus. This flexibility positions the technology as a scalable solution that can adapt to various local agricultural practices and biomass availability.

This research is not conducted in isolation; it is part of a larger collaborative initiative linking several Department of Energy Bioenergy Research Centers. The shared objective encompasses extracting and effectively utilizing lignin for high-value chemical production. Other centers within this network focus on different aspects of lignin processing, ensuring a comprehensive approach toward fully leveraging plant biomass for sustainable energy and materials.

As we stand at the crossroads of energy innovation, this work highlights an important step toward a green energy future. By addressing a significant bottleneck in biomass conversion, Raj and Singh bring us closer to making biofuels a mainstream alternative to fossil fuels. Their research not only champions the idea of using renewable resources for powering our transportation and industrial sectors but also emphasizes the potential of biorefinery systems that yield a variety of useful products.

As the research landscape evolves, it is crucial for scientists to continue exploring innovative pathways that make biofuels more economically viable and environmentally friendly. The advancements in lignin recovery are a testament to the intersection of chemistry, engineering, and sustainable practices that drive the biofuel sector forward.

Ultimately, the success of these pretreatment strategies could pave the way for more efficient biorefineries, where lignin and other components of biomass are not viewed merely as waste but as valuable resources that contribute to a circular economy. With ongoing research and collaboration, the promise of biofuels made from sustainable feedstocks may soon become a reality, presenting an opportunity for a greener, more sustainable planet.

This pioneering work, which has been recognized for its potential impact on the field, will undoubtedly inspire further investigations into the integration of innovative materials and methods for refining bioenergy processes, ensuring that the future of energy remains bright and sustainable.

Subject of Research: Cells
Article Title: Green pretreatment strategies for enhanced microbial lipid fermentation and synergistic high-quality lignin recovery for next-generation integrated biorefineries
News Publication Date: 8-Jan-2026
Web References: Chemical Engineering Journal Advances
References: DOI: 10.1016/j.ceja.2025.101031
Image Credits: Credit: Julia Pollack

Keywords

Biofuels, Biofuels production, Bioengineering, Separation methods, Biomass recalcitrance