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"Ethosomes are ethanol liposomes" was developed by Touitou et al., 1997 are non invasive soft vesicles delivery carriers that enable drugs to reach the deeper layer or the systemic circulation. The aim of present study was to assess the topical potential of ethosomes loaded with melatonin for the prevention of melatonin. It was done by encapsulating the drug in various ethosomal formulations composed of various ratios of ethanol, soya lecithin and cholesterol prepared by cold method. The prepared ethosomal formulations were characterized for particle shape, vesicle size, zeta potential, drug content, % entrapment efficiency (%EE), FTIR, in-vitro drug release study kinetics of drug release and stability. Then optimized formulation was incorporated in gel and evaluated for viscosity, pH, extrudability, homogeneity, skin irritation study, spreadability, FTIR studies, in vitro skin permeation study, flux and stability.