The green and versatile character of deep eutectic solvents (DES) has turned them into significant tools in the development of green and sustainable technologies. For this purpose, their use in polymeric applications has been growing and expanding to new areas of development. The present review aims to summarize the progress in the field of DES applied to polymer science and engineering. It comprises fundamentals studies involving DES and polymers, recent applications of DES in polymer synthesis, extraction and modification, and the early developments on the formulation of DES–polymer products. The combination of DES and polymers is highly promising in the development of new and ‘greener’ materials. Still, there is plenty of room for future research in this field.

The use of water as a component of deep eutectic systems (DES) has raised some questions regarding its influence on the nature of the mixture. Does it form a DES or an aqueous solution and what is the role of water? In this work, the nature of citric acid:L-arginine:water mixtures was explored through phase equilibria studies and spectroscopic analysis. In a first step, PC-SAFT was validated as a predictive tool to model the water influence on the solid liquid equilibria (SLE) of the DES reline using the individual-component approach. Hence, activity coefficients in the ternary systems citric acid:L-arginine:water and respective binary combinations were studied and compared using ePC-SAFT. It was observed that the water-free mixtures citric acid:L-arginine showed positive deviation from Raoult's law, while upon addition of water strong negative deviation from Raoult's law was found, yielding melting depressions around 100 K. Besides these strong interactions, pH was found to become acidic (pH = 3.5) upon water addition, which yields the formation of charged species ([H₂Cit]⁻ and [L-arg]⁺). Thus, the increased interactions between the molecules upon water addition might be caused by several mechanisms such as hydrogen bonding or ionic forces, both being induced by water. For further investigation, the liquid mixtures citric acid:L-arginine:water were studied by FTIR and NMR spectroscopy. FTIR spectra disproved a possible solubility enhancement caused by salt formation between citric acid and L-arginine, while NMR spectra supported the formation of a hydrogen bonding network different from the binary systems citric acid:water and L-arginine:water. Either being a DES or other type of non-ideal solution, the liquefaction of the studied systems is certainly caused by a water-mediator effect based on the formation of charged species and cross interactions between the mixture constituents.

Most nonsteroidal anti-inflammatory drugs (NSAIDs) present poor aqueous solubility, impairing their efficiency in physiological media. In this context, Low Transition Temperature Mixtures (LTTMs) are a promising platform to overcome drugs’ poor solubility, forming therapeutic liquid formulations. In this work, the LTTMs of citric acid:L-arginine:water (C:A:W) and glycerol:sorbitol (G:S) were studied in terms of their features and assessed in terms of their ability to increase the solubility of six NSAIDs in physiological media. The physicochemical properties of LTTMs were characterized by state-of-art techniques commonly used for these systems. The cytotoxicity of G:S was also evaluated in L929 mouse fibroblasts and the viscosity, polarity, and pH properties of the studied mixtures were related to the solubility of NSAIDs. The pH and polarity were the parameters that most influenced the drugs’ solubility. Ibuprofen, naproxen, ketoprofen, indomethacin, and flurbiprofen did not present any solubility improvement in the formulations tested. However, concentrated mixtures of C:A:W or G:S in the physiologic-mimicked media (PBS) rendered a celecoxib solubility 4 and 5 times higher than PBS, respectively. These therapeutic liquid formulations of celecoxib in C:A:W or G:S can be a promising tool to increase celecoxib’s therapeutic efficiency in local applications.

Viscosupplementation consists of hyaluronic acid (HA) intra-articular injections, commonly applied for osteoarthritis treatment while non-steroidal anti-inflammatory drugs (NSAIDs) are widely administered for pain relief. Here, HA and a NSAID (celecoxib) were combined in a formulation based on a low transition temperature mixture (LTTM) of glycerol:sorbitol, reported to increase celecoxib's solubility, thus rendering a potential alternative viscosupplement envisioning enhanced therapeutic efficiency. The inclusion of glucosamine, a cartilage precursor, was also studied. The developed formulations were assessed in terms of rheological properties, crucial for viscosupplementation: the parameters of crossover frequency, storage (G') and loss (G'') moduli, zero-shear-rate viscosity, stable viscosity across temperatures, and shear thinning behaviour, support viscoelastic properties suitable for viscosupplementation. Additionally, the gels biocompatibility was confirmed in chondrogenic cells (ATDC5). Regarding drug release studies, high and low clearance scenarios demonstrated an increased celecoxib (CEX) release from the gel (6 to 73-fold), compared to dissolution in PBS. The low clearance setup presented the highest and most sustained CEX release, highlighting the importance of the gel structure in CEX delivery. NMR stability studies over time demonstrated the LTTM+HA+CEX (GHA+CEX) gel as viable candidate for further in vivo evaluation. In sum, the features of GHA+CEX support its potential use as alternative viscosupplement.

Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability worldwide. Current therapies include pain relief with oral uptake of non-steroidal anti-inflammatory drugs (NSAIDs) and intra-articular injections of hyaluronic acid (HA), to restore the lubricant and protective properties of the joint (viscosupplementation). The administration of both therapies is limited, especially for NSAIDs, given the systemic side-effects. This work intended to explore the potential of a novel injectable gel for osteoarthritis treatment consisting of hyaluronic acid (HA) combined with celecoxib (CEX) incorporated in a glycerol:sorbitol (GS)-based Low Transition Temperature Mixture (LTTM) for enhanced bioavailability. The efficacy of HA+GS+CEX versus HA, HA+CEX and saline control was tested in a post-traumatic osteoarthritis rat model (female Sprague-Dawley rats, n = 6 per group), induced by unilateral anterior cruciate ligament transection and partial medial meniscectomy (ACLt+pMMx). Outcome measures included knee edema, pain-associated behaviour, systemic CEX levels, bone changes as detected by micro-computed tomography, joint degeneration by Mankin score and synovitis by Krenn score. No changes were observed in knee edema between treatments. All HA-containing formulations effectively reduced synovitis, and alleviated pain-associated behaviour. HA+GS+CEX injection limited the peak CEX systemic exposure, prevented the loss of integrity of the subchondral bone plate, and inhibited cartilage degeneration. Overall, although all HA-based formulations reduced pain and inflammation, only the combination of HA+GS+CEX inhibited joint degeneration, suggesting an added therapeutic benefit over HA or HA+CEX alone.