Topical niacinamide enhances hydrophobicity and resilience of corneocyte envelopes on different facial locations The stratum corneum (SC) undergoes a variety of catabolic and anabolic reactions towards its outer surface layers in preparation for its external assault from the terrestrial environment [1]. These events are essential for the formation of a healthy barrier. Key is the maturation of the corneocyte envelope (CE) (Fig. 1). Morphologically, CE's appear fragile in the deeper layers of the SC and more rigid in the outer layers, the mechanics of which have been confirmed with several biomechanical approaches [2]. Early methods to assessing the maturity of the CE's were based upon staining with tetramethylrhodamine isothiocyanate (TRITC) where rigid CEs stain more intensely than fragile ones [3]. Later, their protein content was assessed by involucrin immunochemistry and their lipid content by Nile red staining which was then expressed as a ratio [4-9]. Using these approaches, improvements in CE maturity of the volar forearm and the legs have been observed with moisturizers containing glycerol [3,10] and niacinamide [11]. We have recently published on the regional complexity of facial skin using a variety of bio-instrumental techniques [12,13] and also developed new CE maturation assays to further probe the corneocyte lipid envelope (CLE) hydrophobicity and corneocyte protein envelope (CPE) structural integrity as independent parameters [14]. These findings prompted us to assess the effect of niacinamide in a 4-week placebo-controlled, randomized topical study on these biochemical and physical parameters on several facial skin sites in young (n = 24, 20.8 AE 1.7 years old) and old Caucasian study participants (n = 24, 57.5 AE 2.9 years old) living in Pretoria, South Africa. The study was approved by the School of Health Care Sciences Research Committee (SRC) together with the Medunsa Campus Research and Ethics Committee (MREC), South Africa, and took place from July to September 2016. All participants provided written informed consent before start of the study. After a three day wash-out phase, either the vehicle or the test cream including 3% of niacinamide (Table 1) were applied twice daily (morning and evening) onto the face after cleansing. The subjects were randomly assigned to use either the vehicle or the test cream. A simple but panellist-acceptable vehicle was chosen with a suitable penetration enhancer, in this case 1-2 propanediol. 2% Figure 1 Model of the corneocyte envelope (CE). An early step in the cornification process is the formation of the intercellular cytoskeleton mainly composed of keratin filaments and filaggrin. Cross-linking of proteins, mainly of loricrin and involucrin form the rigid inner corneocyte protein envelope (CPE). Then, a lipid monolayer, the corneocyte lipid envelope (CLE), is covalently attached to the CPE. The CLE serves as a scaffold for the lamellar organization of the extracellular lipid matrix.