Abstract
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.
Highlights
Natural deep eutectic solvents (NADES; used as both singular and plural in the following) have gained much attention lately for their potential as green solvents, as well as for their unique physicochemical properties [1]
A second dilution series (D2) containing less water was prepared, with a final water content of 40% ± 5 (w/w). This was done to ensure that the water content of the samples was kept below 50%, which has been proposed as the critical limit for H-bond-formation in some NADES [28]
The components and structure of NADES play an important role in their properties and offer a wide range of opportunities for modifications and tailoring of these solvents
Summary
Natural deep eutectic solvents (NADES; used as both singular and plural in the following) have gained much attention lately for their potential as green solvents, as well as for their unique physicochemical properties [1]. Deep eutectic solvents are considered less toxic, inexpensive, environmental friendly, biodegradable and less volatile compared to conventional solvents, such as ionic liquids (ILs) and organic solvents [4] Since their discovery in 2011 [5], NADES have presented a range of possibilities for novel drug delivery systems as they are tunable and thermally and chemically stable [6,7]. NADES could be potential drug carriers in a dermal formulation or possibly in formulations for local administration in the oral cavity [6,16,17] Due to their previously mentioned antimicrobial activity, they would be especially relevant as pharmaceutical vehicles in antimicrobial treatments i.e., of chronic topical infections. Skin is composed of extracellular matrix (e.g., collagen) and the potential interactions of NADES with both the biological membranes and collagen can affect the permeation and retention of active drug molecules. All experiments were performed at 25 °C unless otherwise stated
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