In this work, we explored natural deep eutectic solvents (NADES) for developing translucent NADES-in-oil emulsions (TEs) for cosmetic applications. NADES, composed of lactic acid and glycerol (1:1 and 1:4 ratios), were selected for their natural origin, non-toxicity, and compatibility with living organisms. These green solvents facilitated the extraction of bioactive compounds from Lavandula angustifolia, Corymbia citriodora, Thymus vulgaris, Quercus suber, Allium sativum, and Origanum vulgare. The resulting NADES-extracts were characterized using LC-MS for compound identification and incorporated into TEs formulations. The content of phenolics, flavonoids, chelating power, and the antioxidant activity were assessed for both NADES-extracts an TEs. The produced TEs (50 wt% egg L-α-phosphatidylcholine (EPC), 20 wt% ethanol, 20 wt% olive oil, and 10 wt% NADES/NADES-extracts) effectively hindered the activity of enzymes responsible for skin melanin regulation and aging, namely tyrosinase (IC50 ≈ 0.18 mg/mL for eucalyptus) and elastase (IC50 ≈ 0.23 mg/mL for thyme). Gram-negative bacteria, particularly K. pneumoniae, were found to be more susceptible to NADES-extracts and TE-extracts, resulting in larger zones of inhibition. The study reported no toxic effects in the larval model, with a noticeable decrease (2-fold) in melanization in G. mellonella larvae after TE application. Cytotoxicity results indicated that TEs could be tolerated in skin cells at concentrations up to 5 %. Transdermal testing showed TEs permeation into the skin of 1–5 %, suggesting their use for cosmetic purposes without significant cellular damage. This study highlights the potential of NADES combined with natural extracts as sustainable, non-toxic ingredients in cosmetic formulations, paving the way for innovative skin regeneration products.
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