Cytotoxicity profiling of deep eutectic solvents to human skin cells

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, [N-1111]Cl and [N-4444]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 [N-1111]Cl-based DES showed good biocompatibility for the tested cells. [N-4444]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 [N-1111]Cl-based DES and should be considered as targets for future studies. These results highlight their possible use in cosmetic or pharmaceutical formulations.

keywords

SODIUM-BUTYRATE; IONIC LIQUIDS; TOXICITY; CHLORIDE; EXTRACTION; APOPTOSIS; GROWTH; BIODEGRADABILITY; STABILITY; MIXTURES

subject category

Science & Technology - Other Topics

authors

Macario, IPE; Oliveira, H; Menezes, AC; Ventura, SPM; Pereira, JL; Goncalves, AMM; Coutinho, JAP; Goncalves, FJM

our authors

acknowledgements

Thanks are due for the financial support to CESAM (UID/AMB/50017 - POCI-01-0145-FEDER-007638) to FCT/MCTES through national funds (PIDDAC), and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020. This work was also developed within the scope of the project CICECO-Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT Ref. UID/CTM/50011/2013), financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. This study was funded by FCT through the project PTDC/ATP-EAM/5331/2014 and PTDC/BTM-MAT/31794/2017 (POCI-01-0145-FEDER-031794), and through the individual research grants awarded to I.P.E. Macario (SFRH/BD/123850/2016), A.C. Menezes (BI/CESAM/012/AMB/50017) and A.M.M. Goncalves (SFRH/BPD/97210/2013). J.L. Pereira and H. Oliveira are funded by national funds (OE), through FCT -Fundacao para a Ciencia e a Tecnologia, I.P., in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. A.M.M. Goncalves also acknowledges University of Coimbra for the contract IT057-18-7253 and the research unit MARE (UID/MAR/04292/2013). S.P.M. Ventura acknowledges FCT for the contract IF/00402/2015 under the Investigador FCT 2015 program.

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