AbstractCeramide3 (Cer3) is one of the important components of stratum corneum (SC) lipids with good moisturizing and repairing properties. However, it suffers from (a) poor solubility, (b) easy crystallization and precipitation, and (c) strong polarity and difficulty in transdermal application. This study aimed to load Cer3 into nanoemulsions (NEs) to overcome these mentioned defects. The optimized NEs formulation was prepared by high pressure homogenization method and characterized by several methods. The optimized ceramide3 nanoemulsions (Cer3‐NEs) exhibited a good physico‐chemical stability over 3 months under different conditions, with droplet size of 103.1 nm, PDI of 0.178, zeta potential of −39.09 mV, pH of 6.20 and encapsulation efficiency of 96.39 %. Turbiscan results showed that formulations containing Cer3‐NEs have better stability than those containing free Cer3. The dermal delivery ability of Cer3‐NEs was assessed by Franz diffusion and confocal Raman spectroscopy (CRM). In vitro and in vivo penetration studies showed that Cer3‐NEs serum have almost 2–3 times higher retention in the skin and permeation in the receptor solution compared to serum with free Cer3. The findings show NE is a promising carrier of Cer3 for topical administration in the treatment of dryness and barrier damage due to higher stability and better skin permeability.
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