Correlation between Ionic Liquid Cytotoxicity and Liposome–Ionic Liquid Interactions

Abstract

This study aims at extending the understanding of the toxicity mechanism of ionic liquids (ILs) using various analytical methods and cytotoxicity assays. The cytotoxicity of eight ILs and one zwitterionic compound was determined using mammalian and bacterial cells. The time dependency of the IL toxicity was assessed using human corneal epithelial cells. Hemolysis was performed using human red blood cells and the results were compared with destabilization data of synthetic liposomes upon addition of ILs. The effect of the ILs on the size and zeta potential of liposomes revealed information on changes in the lipid bilayer. Differential scanning calorimetry was used to study the penetration of the ILs into the lipid bilayer. Pulsed field gradient nuclear magnetic resonance spectroscopy was used to determine whether the ILs occurred as unimers, micelles, or if they were bound to liposomes. The results show that the investigated ILs can be divided into three groups based on the cytotoxicity mechanism: cell wall disrupting ILs, ILs exerting toxicity through both cell wall penetration and metabolic alteration, and ILs affecting solely on cell metabolism.

Solvent Welding and Imprinting Cellulose Nanofiber Films Using Ionic Liquids

“…Where It is the total intensity of the (0 0 2) peak for cellulose I and Ia is the intensity assigned to the amorphous cellulose. [51][52][53] . In addition, the IL welded CNFFs have changed their UV-Vis transmittance, suggesting that in some cases, IL might also remain attached to the films.…”

Mechanisms of action of ionic liquids on living cells: the state of the art

“… Membrane damage has been observed in red blood cells (RBC) incubated in [C 4 mim][Br], [C 10 mim][BF 4 ], and [BTDA][Cl] (Thamke et al 2017 ). Destabilization of the plasma cellular membrane of human corneal epithelial HCE cells and hemolysis of RBCs have been observed after incubation in [P 14444 ][Cl] and [P 14444 ][OAc] (Ruokonen et al 2018 ). In the same study, it has been shown that these two ILs switch the zeta potential of model lipid liposomes from negative to positive, evidencing a strong and possibly irreversible sorption of the ILs into the liposome.…”

A combined targeted/untargeted LC-MS/MS-based screening approach for mammalian cell lines treated with ionic liquids: Toxicity correlates with metabolic profile

“…Human corneal epithelial (HCE) cells were employed as representative model cells. A wide variety of ILs were selected and the metabolic profiles measured after incubation of the HCE cells with ILs at concentration levels corresponding to their median effective concentration (EC 50 ) values [4]. Here we will demonstrate that there is a correlation between the changes in the metabolic profiles and the toxicity of the ILs.…”

“…Since they are non-flammable, non-explosive, and non-volatile, they are used in many applications, also owing to their large range of solubilities and miscibilities. Their lack of biodegradability, however, renders toxicity studies imperative [4,5]. This matter is complicated because of the high structural variability and large number of existing ILs, requiring a differentiated picture of toxic effects of ILs [1,6,7].…”