A New Cosmeceutical Approach for Mature Skin: Antioxidant Activity, In Vitro Permeation, and Preliminary Clinical Efficacy of Melatonin-N-Acetylcysteine Creams.

Skin ageing is associated with oxidative stress, mitochondrial dysfunction, extracellular matrix alterations, and impaired barrier function, supporting interest in antioxidant cosmeceuticals for mature skin. This study investigated the antioxidant activity of melatonin and N-acetylcysteine, the in vitro permeation of melatonin from different cream formulations, and their preliminary clinical performance in women aged 55-65 years. Antioxidant activity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)/Trolox equivalent antioxidant capacity (ABTS/TEAC) assays. Melatonin permeation across Strat-M® membranes was evaluated using Franz diffusion cells and quantified by a validated high-performance liquid chromatography method coupled with a photodiode-array detection (HPLC-PDA) method. Clinical changes were assessed over 28 days using the Glogau wrinkle scale and a lower facial ptosis scale. N-acetylcysteine exhibited greater antioxidant activity than melatonin in the DPPH assay, with half-maximal inhibitory concentration (IC50) values of 5.96 ± 1.02 and 530.11 ± 48.63 µg/mL, respectively. Melatonin permeation varied according to formulation composition, with cumulative amounts after 24 h ranging from 81.27 ± 17.47 to 1043.48 ± 33.43 µg/cm2. Reductions in periocular wrinkle and lower facial ptosis scores were observed after 28 days. These preliminary findings support further investigation of melatonin-N-acetylcysteine creams for mature skin. However, the present membrane model did not assess cutaneous retention, and the clinical observations require confirmation in larger, controlled studies.