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Chronic wounds pose a significant and growing global health challenge, affecting millions of individuals and often leading to prolonged suffering and increased healthcare costs. A major barrier to effective healing is wound infection, which disrupts the natural repair process and contributes to the chronicity. Therefore, innovative strategies for infection control are urgently required. Deep Eutectic Solvents (DESs) have recently gained attention as promising drug delivery systems owing to their multifunctional properties. In addition to serving as penetration enhancers that improve drug permeation, DESs exhibit intrinsic antimicrobial and antibiofilm activities, making them attractive candidates for managing infected wounds. This review highlights the fundamentals of DESs in the context of chronic wound management. It provides an overview of the wound healing process, pathophysiology of chronic wounds, and the role of biofilms in persistent infections. It further explores the dual role of DESs as penetration enhancers and antibiofilm agents, summarizing the recent DES-based formulations under investigation. Finally, this review discusses the current challenges and future prospects of integrating DESs into clinical practice. Collectively, DESs represent novel and versatile therapeutic platforms that have the potential to transform the treatment landscape of chronic wound healing.

Deep eutectic solvents are an exciting class of designer solvents that are increasingly gaining popularity. Deep eutectic solvents based on amino acids are particularly interesting for biomedical applications due to their potential low toxicity. However, very few have been reported to date, and only one of these has been comprehensively studied, made from a combination of proline and glycerol. Here, we report for the first time a systematic investigation into amino acid-based deep eutectic solvents, with a particular focus on the structural features of amino acids that promote eutectic formation and their influence on viscosity, refractive index, surface tension and thermal behavior. Of the 22 amino acids (and related compounds) examined, only 3 (lysine, arginine and, as previously reported, proline) formed stable homogenous liquids in combination with glycerol or ethylene glycol. For these mixtures, it was found that the second component (glycerol or ethylene glycol) had a much more significant influence on the physical properties than the identity of the amino acid. Most significantly, it was found that far fewer amino acids readily formed deep eutectic solvents than has been generally assumed. This is the first work to systematically characterize deep eutectic solvents based on amino acids and, as such, paves the way for future biomedical applications of these solvents.

Cryopreservation is a well-established method for extending platelet shelf-life and addressing supply shortages. Traditionally, this involves dimethyl sulfoxide (DMSO) as a cryoprotective agent (CPA), but recent studies suggest that using controlled rate freezing (CRF) with only NaCl may offer a less toxic alternative. To explore further optimization, this study assessed whether adding 10% choline chloride–glycerol, a deep eutectic solvent (DES), could enhance platelet quality in CRF/NaCl cryopreservation. Ten double-dose buffy coat platelet units were divided into test (DES-treated) and control (NaCl-only) groups. After DES exposure (10% for 20 min), all units were prepared using the NaCl protocol and frozen at −80 °C with CRF equipment, then stored for over 90 days. Upon thawing and reconstitution in AB plasma, no significant differences were observed in platelet content post-thaw between control and test units (255 ± 43 vs. 257 ± 41 × 109/unit), post-thaw recovery (>85%): respectively, Δψ (JC-1% pos 63 ± 15 vs. 68 ± 17), LDH (% of total 10 ± 6 vs. 9 ± 6), (CD63% 77 ± 9 vs. 82 ± 7), (CD62P % 72 ± 15 vs. 76 ± 11), (CD42b % 78 ± 9 vs. 80 ± 9), (CD61% 79 ± 9 vs. 78 ± 9), (CD41% 81 ± 11 vs. 83 ± 7), (PAC-1% 33 ± 10 vs. 32 ± 8), (Pecam-1% 78 ± 11 vs. 80 ± 8), (GPIV % 72 ± 10 vs. 74 ± 11), (LAMP-1% 26 ± 14 vs. 11 ± 9), (MPCD61+ % 41 ± 11 vs. 46 ± 10), (ROTEM CT 56 ± 7 vs. 55 ± 6), (ROTEM CFT 110 ± 70 vs. 106 ± 67) and (ROTEM MCF 35 ± 6 vs. 36 ± 6). These findings support the feasibility of CPA-free CRF-based platelet cryopreservation while maintaining functional integrity.

Polysaccharides, which can be affected by different preparations, play a crucial role in the biological function of Paecilomyces hepiali (PHPS) as a health food. To explore high-valued polysaccharides and reduce the negative influence of human involvement, a green tailorable deep eutectic solvent (DES) was applied to optimize the extraction of polysaccharides (PHPS-D), followed by the evaluation of the structural properties and immunomodulation by comparison with the hot-water method (PHPS-W). The results indicated that the best system for PHPS-D was a type of carboxylic acid-based DES consisting of choline chloride and succinic acid in the molar ratio of 1:3, with a 30% water content. The optimal condition was as follows: liquid–solid ratio of 50 mL/g, extraction temperature of 85 °C, and extraction time of 1.7 h. The actual PHPS-D yield was 12.78 ± 0.17%, which was obviously higher than that of PHPS-W. The structural characteristics suggested that PHPS-D contained more uronic acid (22.34 ± 1.38%) and glucose (40.3 ± 0.5%), with a higher molecular weight (3.26 × 105 g/mol) and longer radius of gyration (78.2 ± 3.6 nm), as well as extended chain conformation, compared with PHPS-W, and these results were confirmed by AFM and SEM. Immunomodulatory assays suggested that PHPS-D showed better performance than PHPS-W regarding pinocytic activity and the secretion of NO and pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) by activating the corresponding mRNA expression in RAW264.7 cells. This study showed that carboxylic acid-based DES could be a promising tailorable green system for acidic polysaccharide preparation and the valorization of P. hepiali in functional foods.

Proteins are among the most common therapeutics for the treatment of diabetes, autoimmune diseases, cancer, and metabolic diseases, among others. Despite their common use, current protein therapies, most of which are injectables, have several limitations. Large proteins such as monoclonal antibodies (mAbs) suffer from poor absorption after subcutaneous injections, thus forcing their administration by intravenous injections. Even small proteins such as insulin suffer from slow pharmacokinetics which poses limitations in effective management of diabetes. Here, a deep eutectic‐based delivery strategy is used to offer a generalized approach for improving protein absorption after subcutaneous injections. The lead formulation enhances absorption of mAbs after subcutaneous injections by ≈200%. The same composition also improves systemic absorption of subcutaneously injected insulin faster than Humalog, the current gold‐standard of rapid acting insulin. Mechanistic studies reveal that the beneficial effect of deep eutectics on subcutaneous absorption is mediated by their ability to reduce the interactions of proteins with the subcutaneous matrix, especially collagen. Studies also confirm that these deep eutectics are safe for subcutaneous injections. Deep eutectic‐based formulations described here open new possibilities for subcutaneous injections of therapeutic proteins. Here the use of deep eutectic solvents in biologic formulations is reported to improve the pharmacokinetic properties of insulin and monoclonal antibodies. The underlying mechanisms are reported and the safety of deep eutectic biologics formulations in a rodent model is evaluated.

Deep eutectic solvents have emerged in green chemistry only seventeen years ago and yet resulted in a plethora of publications covering various research areas and diverse fields of application. Deep eutectic solvents appear as promising alternatives to conventional organic solvents due to their straightforward preparation using highly accessible and natural compounds. They display also high tunability. Here we present the classification and preparation methods of deep eutectic solvents. We detail their physicochemical properties such as phase behavior, density, viscosity, ionic conductivity, surface tension, and polarity. Properties are controlled by the choice of the forming compounds, molar ratio, temperature, and water content.

‘Ideal’ solvents in biocatalysis have to fulfill a large number of requirements, such as high substrate solubility, high enzyme activity and stability, and positive effects on reaction equilibrium. In the past decades, many enzymatic synthesis routes in water-based and nonaqueous (organic solvents, ionic or supercritical fluids) reaction media have been developed. However, no solvent meets every demand for different reaction types at the same time, and there is still a need for novel solvents suited for different reaction types and applications. Deep eutectic solvents (DESs) have recently been evaluated as solvents in different biocatalytic reactions. They can improve substrate supply, conversion, and stability. The best results were obtained when the DES is formed by the substrates of an enzymatic reaction. A wide range of inexpensive renewables can be used as components of deep eutectic solvents; therefore, the solvents are often biodegradable, nontoxic, nonvolatile, and nonflammable. A broad range of enzymatic and chemo-enzymatic synthesis reactions can be performed in deep eutectic solvents. Most of the reactions, covering transesterifications, epoxidations, and C–C bond formations, are catalyzed by lipases. Deep eutectic solvents can be used to enable new biocatalytic synthesis routes that cannot be realized in conventional reaction media (i.e., aqueous buffers). Components of deep eutectic solvents can be used as substrate and solvent at the same time; this virtually solvent-free approach enables processes with high substrate conversion and high atom efficiency.

Deep eutectic solvents (DESs) are one of the most rapidly evolving types of solvents, appearing in a broad range of applications, such as nanotechnology, electrochemistry, biomass transformation, pharmaceuticals, membrane technology, biocomposite development, modern 3D-printing, and many others. The range of their applicability continues to expand, which demands the development of new DESs with improved properties. To do so requires an understanding of the fundamental relationship between the structure and properties of DESs. Computer simulation and machine learning techniques provide a fruitful approach as they can predict and reveal physical mechanisms and readily be linked to experiments. This review is devoted to the computational research of DESs and describes technical features of DES simulations and the corresponding perspectives on various DES applications. The aim is to demonstrate the current frontiers of computational research of DESs and discuss future perspectives.

The increasing antibiotic resistance towards a panel of microorganisms is one of the public health concerns. For this reason, the search for alternatives to the widely used antibiotic has been undertaken. In the era of sustainable chemistry, deep eutectic solvents (DESs) have emerged as promising antimicrobial agents. These solvents possess several advantages such as low volatility, low flammability, ease of preparation, and typically low cost of production. These properties make DES suitable for various applications, including extraction of biomolecules and preparation of cosmetics. Natural DESs (NADESs) are special category of DESs prepared from natural sources, which matched the recent trends of leaning back to nature, and decreasing dependence on synthetic precursors. NADES can be prepared by heating and stirring, freeze-drying, evaporation, grinding, and ultrasound-assisted and microwave-assisted synthesis. Utilizing NADESs as an alternative to traditional antibiotics, which become ineffective over time due to bacterial resistance, holds great promise for these reasons. This review aims to discuss the antimicrobial properties of multiple NADESs, including antibacterial and antifungal activities. To the best of our knowledge, this review is the first literature survey of the antimicrobial activities of NADESs. Key points • Natural deep eutectic solvents are promising antimicrobial alternative to antibiotics • NADES holds high potential for their activity against bacterial resistance • NADES have also substantial antifungal activities

The roots of the medicinal plant Aralia elata are rich in biologically active natural products, with triterpene saponins constituting one of their major groups. These metabolites can be efficiently extracted by methanol and ethanol. Due to their low toxicity, natural deep eutectic solvents (NADES) were recently proposed as promising alternative extractants for the isolation of natural products from medicinal plants. However, although NADES-based extraction protocols are becoming common in routine phytochemical work, their application in the isolation of triterpene saponins has not yet been addressed. Therefore, here, we address the potential of NADES in the extraction of triterpene saponins from the roots of A. elata. For this purpose, the previously reported recoveries of Araliacea triterpene saponins in extraction experiments with seven different acid-based NADES were addressed by a targeted LC-MS-based quantitative approach for, to the best of our knowledge, the first time. Thereby, 20 triterpene saponins were annotated by their exact mass and characteristic fragmentation patterns in the total root material, root bark and root core of A. elata by RP-UHPLC-ESI-QqTOF-MS, with 9 of them being identified in the roots of this plant for the first time. Triterpene saponins were successfully extracted from all tested NADES, with the highest efficiency (both in terms of the numbers and recoveries of individual analytes) achieved using a 1:1 mixture of choline chloride and malic acid, as well as a 1:3 mixture of choline chloride and lactic acid. Thereby, for 13 metabolites, NADES were more efficient extractants in comparison with water and ethanol. Our results indicate that new, efficient NADES-based extraction protocols, giving access to high recoveries of triterpene saponins, might be efficiently employed in laboratory practice. Thus, our data open the prospect of replacing alcohols with NADES in the extraction of A. elata roots.