Cytotoxicity profiling of deep eutectic solvents to human skin cells

I P E Macário,A C Menezes,J L Pereira,J A P Coutinho,H Oliveira,S P M Ventura,A M M Gonçalves,F J M Gonçalves

doi:10.1038/s41598-019-39910-y

Abstract

The tailor-made character of deep eutectic solvents (DES) turns them very attractive to be used in several applications, including in health-related areas such as pharmaceutical, nutraceutical, and cosmetic industries. However, although DES has been touted as “green” solvents, several works proved that their potential toxicity should not be neglected. Using the premise of DES applicability in the cosmetic and pharmaceutical sectors, we chose two cell lines to work as a skin model (keratinocytes HaCaT and tumor melanocytes MNT-1), to assess DES cytotoxicity. The effect of three different hydrogen bond acceptors (HBA) ([Chol]Cl, [N1111]Cl and [N4444]Cl) and three different hydrogen bond donors (HBD) (hexanoic and butanoic acid, ethylene glycol, 1-propanol and urea) were evaluated through a common viability assay (MTT assay). Results were promising since [Chol]Cl and [N1111]Cl- based DES showed good biocompatibility for the tested cells. [N4444]Cl-based DES, however, showed cytotoxicity for both cell lines, with the HBA being the driver of the toxicity. Interestingly, some compounds increased cell viability in the HaCaT cell line, namely [Chol]Cl, ethylene glycol, hexanoic acid, urea, and all [Chol]Cl and [N1111]Cl-based DES and should be considered as targets for future studies. These results highlight their possible use in cosmetic or pharmaceutical formulations.

Highlights

The field of “designer solvents” such as ionic liquids (IL) and deep eutectic solvents (DES) has been growing in the past decades, under the scope of “Green Chemistry”, which promotes the design and application of chemical products and processes that could reduce or preferentially eliminate the use and generation of hazardous substances[1]
Regarding the hydrogen bond donors (HBD), only butanoic acid showed a toxic effect for both cell types. [N1111]Cl did not exert any effect in cell viability in MNT-1, but increased the viability of HaCaT at 50 μg.mL−1 and significantly decreased it at 500 μg.mL−1
Ethylene glycol caused the higher increase in cell viability especially in HaCaT cells, with some treatments reaching 40% of increase in cell viability compared to the control

Summary

Introduction

The field of “designer solvents” such as ionic liquids (IL) and deep eutectic solvents (DES) has been growing in the past decades, under the scope of “Green Chemistry”, which promotes the design and application of chemical products and processes that could reduce or preferentially eliminate the use and generation of hazardous substances[1]. DES were firstly developed in 2003 by combining urea and cholinium chloride[2] These are prepared through the mixing of two or three different starting materials (e.g., quaternary ammonium salts, amides, organic acids, polyalcohols) forming an eutectic mixture based on hydrogen bonding interactions between a hydrogen bond donor (HBD) and an acceptor (HBA). DES were initially considered as “green solvents”, mainly due to the benign nature of their constituents, only a few studies are available that assessed their toxic potential, either regarding their ecotoxicity[6,19,20,21,22,23,24,25,26,27], or their cytotoxicity[22,23,28,29,30]. Two alcohols and two acids differing in their alkyl chain length, and number of functional groups, as well as an amine (urea) were selected to represent the most commonly functional groups applied as HBD for DES formulation

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