Interactions of natural deep eutectic solvents (NADES) with artificial and natural membranes

Natural deep eutectic solvents (NADES) are a third type of liquids, apart from water and lipids. NADES show promise as drug carriers in dermal formulations or formulations for local administration in the oral cavity due to their low toxicity, tunability and biodegradability as well as their solubilizing and stabilizing properties. However, a thorough investigation of their effects in a biological system is needed. The present study aimed to investigate the physicochemical properties of six selected NADES and dilutions thereof. Further, the suitability of NADES as vehicles in topical preparations was evaluated through the application of liposome model membranes and ex vivo pig skin models. The effects of NADES on the membrane stability of egg-phosphatidylcholine (Egg-PC) liposomes and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine 16:0 PC (DPPC) liposomes were investigated by physical stability studies, membrane permeability studies, calorimetric analysis and visual representation by transmission electron microscopy (TEM). The liposomes appeared in most cases physically stable for 24 h in NADES, although there were changes in size and morphology most likely related to increased osmolality. Some NADES were also able to disaggregate formed DPPC liposome aggregates. The ex vivo permeation studies indicated a slightly reduced permeability of chloramphenicol through the pig skin after NADES application, which most likely was caused by hydrogen bonding between the NADES and proteins in the skin based on FT-IR-results. Altogether, our findings suggest that NADES are promising drug carriers in new drug delivery systems for topical applications. (C) 2021 The Author(s). Published by Elsevier B.V.