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Solubility, bioavailability, permeation, polymorphism, and stability concerns associated to solid-state pharmaceuticals demand for effective solutions. To overcome some of these drawbacks, ionic liquids (ILs) have been investigated as solvents, reagents, and anti-solvents in the synthesis and crystallization of active pharmaceutical ingredients (APIs), as solvents, co-solvents and emulsifiers in drug formulations, as pharmaceuticals (API-ILs) aiming liquid therapeutics, and in the development and/or improvement of drug-delivery-based systems. The present review focuses on the use of ILs in the pharmaceutical field, covering their multiple applications from pharmaceutical synthesis to drug delivery. The most relevant research conducted up to date is presented and discussed, together with a critical analysis of the most significant IL-based strategies in order to improve the performance of therapeutics and drug delivery systems.

The use of ionic liquids and deep eutectic solvents in biomedical applications has grown dramatically in recent years due to their unique properties and their inherent tunability. This review will introduce ionic liquids and deep eutectics and discuss their biomedical applications, namely solubilization of drugs, creation of active pharmaceutical ingredients, delivery of pharmaceuticals through biological barriers, stabilization of proteins and other nucleic acids, antibacterial agents, and development of new biosensors. Current challenges and future outlooks are discussed, including biocompatibility, the potential impact of the presence of impurities, and the importance of understanding the microscopic interactions in ionic liquids in order to design task‐specific solvents. This review covers historical and recent advances of ionic liquids within the field of biomedicine. The article focuses on solubilization of drugs, active pharmaceutical ingredient ionic liquids, drug delivery, nanocarriers, protein stabilization, antimicrobial agents, and biosensing. The review also provides the future outlook and challenges for ionic liquids in the field of biomedical science.

Ionic liquids (ILs) are solvents with salt structures. Typically, they contain organic cations (ammonium, imidazolium, pyridinium, piperidinium or pyrrolidinium), and halogen, fluorinated or organic anions. While ILs are considered to be environmentally-friendly compounds, only a few reasons support this claim. This is because of high thermal stability, and negligible pressure at room temperature which makes them non-volatile, therefore preventing the release of ILs into the atmosphere. The expansion of the range of applications of ILs in many chemical industry fields has led to a growing threat of contamination of the aquatic and terrestrial environments by these compounds. As the possibility of the release of ILs into the environment s grow systematically, there is an increasing and urgent obligation to determine their toxic and antimicrobial influence on the environment. Many bioassays were carried out to evaluate the (eco)toxicity and biodegradability of ILs. Most of them have questioned their “green” features as ILs turned out to be toxic towards organisms from varied trophic levels. Therefore, there is a need for a new biodegradable, less toxic “greener” ILs. This review presents the potential risks to the environment linked to the application of ILs. These are the following: cytotoxicity evaluated by the use of human cells, toxicity manifesting in aqueous and terrestrial environments. The studies proving the relation between structures versus toxicity for ILs with special emphasis on directions suitable for designing safer ILs synthesized from renewable sources are also presented. The representants of a new generation of easily biodegradable ILs derivatives of amino acids, sugars, choline, and bicyclic monoterpene moiety are collected. Some benefits of using ILs in medicine, agriculture, and the bio-processing industry are also presented.

This paper reviews the primary literature reporting the use of ionic liquids (ILs) in optical sensing technologies. The optical chemical sensors that have been developed with the assistance of ILs are classified according to the type of resultant material. Key aspects of applying ILs in such sensors are revealed and discussed. They include using ILs as solvents for the synthesis of sensor matrix materials; additives in polymer matrices; matrix materials; modifiers of the surfaces; and multifunctional sensor components. The operational principles, design, texture, and analytical characteristics of the offered sensors for determining CO2, O2, metal ions, CN−, and various organic compounds are critically discussed. The key advantages and disadvantages of using ILs in optical sensing technologies are defined. Finally, the applicability of the described materials for chemical analysis is evaluated, and possibilities for their further modernization are outlined.

Cholinium amino acid ionic liquids ([Ch][AA] ILs), which are wholly composed of renewable biomaterials, have recently been demonstrated to have very promising properties for applications in organic synthesis and biomass pretreatment. In this work, the toxicity of these ILs toward enzymes and bacteria was assessed, and the effect of the anion on these properties is discussed. The inhibitory potentials of this type of ILs to acetylcholinesterase were weaker approximately an order of magnitude than the traditional IL 1-butyl-3-methylimidazolium tetrafluoroborate. Additionally, the [Ch][AA] ILs displayed low toxicity toward the bacteria tested. Furthermore, the biodegradability of the [Ch][AA] ILs was evaluated via the closed bottle and CO(2) headspace tests using wastewater microorganisms. All the ILs were classified as 'readily biodegradable' based on their high levels of mineralization (62-87%). The presence of extra carboxyl or amide groups on the amino acid side chain rendered the ILs significantly more susceptible to microbial breakdown. In addition, for most of the [Ch][AA] ILs, low toxicity correlated with good biodegradability. The low toxicity and high biodegradability of these novel [Ch][AA] make them promising candidates for use as environmentally friendly solvents in large-scale applications.

A hydrophobic gadolinium-based magnetic ionic liquid (MIL) was investigated for the first time as an extraction solvent in dispersive liquid–liquid microextraction (DLLME). The tested MIL was composed of trihexyl(tetradecyl)phosphonium cations and paramagnetic gadolinium chloride anions. The prepared MIL showed low water miscibility, reasonable viscosity, markedly high magnetic susceptibility, adequate chemical stability, low UV background, and compatibility with reversed-phase HPLC solvents. These features resulted in a more efficient extraction than the corresponding iron or manganese analogues. Accordingly, the overall method sensitivity and reproducibility were improved, and the analysis time was reduced. The applicability of the proposed MIL was examined through the microextraction of four sartan antihypertensive drugs from aqueous samples followed by reversed-phase HPLC with UV detection at 240 nm. The DLLME procedures were optimized for disperser solvent type, MIL mass, disperser solvent volume, as well as acid, base, and salt addition. The limits of quantitation (LOQs) obtained with the analysis of 1.2-mL samples after DLLME and HPLC were 80, 30, 40, and 160 ng/mL for azilsartan medoxomil, irbesartan, telmisartan, and valsartan, respectively. Correlation coefficients were greater than 0.9988 and RSD values were in the range of 2.48–4.07%. Under the optimized microextraction conditions and using a 5-mL sample volume, enrichment factors were raised from about 40 for all sartans using a 1.2-mL sample to 175, 176, 169, and 103 for azilsartan medoxomil, irbesartan, valsartan, and telmisartan, respectively. The relative extraction recoveries for the studied sartans in river water varied from 82.5 to 101.48% at a spiked concentration of 0.5 μg/mL for telmisartan and irbesartan and 1 μg/mL for azilsartan medoxomil and valsartan.

Green Chemistry plays a more and more important role in implementing rules of sustainable development to prevent environmental pollution caused by technological processes, while simultaneously increasing the production yield. Ionic liquids (ILs) and deep eutectic solvents (DESs) constitute a very broad group of substances. Apart from many imperfections, ILs and DESs have been the most promising discoveries in the world of Green Chemistry in recent years. The main advantage of ILs is their unique physicochemical properties—they are very desirable from the technological point of view, but apart from these benefits, ILs appear to be highly toxic towards organisms from different trophic levels. DES areas of usage are very spread, because they cover organic synthesis, extraction processes, electrochemistry, enzymatic reactions and many others. Moreover, DESs seem to be a less toxic alternative to ionic liquids. New possibilities of applications and future development trends are sought and presented, including such important solutions of life branches as pharmaceuticals’ production and medicine.

Perovskite solar cells (PSCs) are among the most promising photovoltaic technologies owing to their exceptional optoelectronic properties 1 , 2 . However, the lower efficiency, poor stability and reproducibility issues of large-area PSCs compared with laboratory-scale PSCs are notable drawbacks that hinder their commercialization 3 . Here we report a synergistic dopant-additive combination strategy using methylammonium chloride (MACl) as the dopant and a Lewis-basic ionic-liquid additive, 1,3-bis(cyanomethyl)imidazolium chloride ([Bcmim]Cl). This strategy effectively inhibits the degradation of the perovskite precursor solution (PPS), suppresses the aggregation of MACl and results in phase-homogeneous and stable perovskite films with high crystallinity and fewer defects. This approach enabled the fabrication of perovskite solar modules (PSMs) that achieved a certified efficiency of 23.30% and ultimately stabilized at 22.97% over a 27.22-cm 2 aperture area, marking the highest certified PSM performance. Furthermore, the PSMs showed long-term operational stability, maintaining 94.66% of the initial efficiency after 1,000 h under continuous one-sun illumination at room temperature. The interaction between [Bcmim]Cl and MACl was extensively studied to unravel the mechanism leading to an enhancement of device properties. Our approach holds substantial promise for bridging the benchtop-to-rooftop gap and advancing the production and commercialization of large-area perovskite photovoltaics. A synergistic dopant-additive combination strategy using methylammonium chloride as the dopant and a Lewis-basic ionic-liquid additive is shown to enable the fabrication of perovskite solar modules achieving record certified performance and long-term operational stability.

With the rise in diabetes mellitus cases worldwide and lack of patient adherence to glycemia management using injectable insulin, there is an urgent need for the development of efficient oral insulin formulations. However, the gastrointestinal tract presents a formidable barrier to oral delivery of biologics. Here we report the development of a highly effective oral insulin formulation using choline and geranate (CAGE) ionic liquid. CAGE significantly enhanced paracellular transport of insulin, while protecting it from enzymatic degradation and by interacting with the mucus layer resulting in its thinning. In vivo, insulin-CAGE demonstrated exceptional pharmacokinetic and pharmacodynamic outcome after jejunal administration in rats. Low insulin doses (3–10 U/kg) brought about a significant decrease in blood glucose levels, which were sustained for longer periods (up to 12 hours), unlike s.c. injected insulin. When 10 U/kg insulin-CAGE was orally delivered in enterically coated capsules using an oral gavage, a sustained decrease in blood glucose of up to 45% was observed. The formulation exhibited high biocompatibility and was stable for 2 months at room temperature and for at least 4 months under refrigeration. Taken together, the results indicate that CAGE is a promising oral delivery vehicle and should be further explored for oral delivery of insulin and other biologics that are currently marketed as injectables.

Ionic liquids (ILs) were initially hailed as a green alternative to traditional solvents because of their almost non-existent vapor pressure as ecological replacement of most common volatile solvents in industrial processes for their damaging effects on the environment. It is common knowledge that they are not as green as desired, and more thought must be put into the biological consequences of their industrial use. Still, compared to the amount of research studying their physicochemical properties and potential applications in different areas, there is a scarcity of scientific papers regarding how these substances interact with different organisms. The intent of this review was to compile the information published in this area since 2015 to allow the reader to better understand how, for example, bacteria, plants, fish, etc., react to the presence of this family of liquids. In general, lipophilicity is one of the main drivers of toxicity and thus the type of cation. The anion tends to play a minor (but not negligible) role, but more research is needed since, owing to the very nature of ILs, except for the most common ones (imidazolium and ammonium-based), many of them are subject to only one or two articles.