title: Influence of niacinamide containing formulations on the molecular and biophysical properties of the stratum corneum.
abstract: Niacinamide-containing moisturisers are known be efficacious in alleviating dry skin conditions and improving stratum corneum (SC) barrier function. However, the mechanisms of action of niacinamide at the molecular level in the SC are still not well understood. Previously, we have reported the development of novel methods to probe SC barrier properties in vivo. The aim of the present study was to characterise changes in Trans Epidermal Water Loss (TEWL), corneocyte surface area and maturity, selected protease activities and SC thickness after repeated application of a simple vehicle containing niacinamide. A commercial formulation was also included as a reference. The left and right mid-volar forearms of 20 healthy volunteers were used as study sites, to which topical formulations were applied twice daily for 28 days. After successive tape-stripping, corneocyte maturity and surface area were assessed. In addition, activity of the desquamatory kallikrein (KLK) protease enzymes KLK5 and KLK7, and tryptase and plasmin (implicated in inflammatory process) were measured using a fluorogenic probe assay. The amount of protein removed and TEWL were also recorded. SC thickness before and after treatment was determined using Confocal Raman Spectroscopy (CRS). Overall (i) corneocyte maturity and surface area decreased with increasing number of tape strips, (ii) activity of both the desquamatory and inflammatory enzymes was highest in the outer layers of the SC and decreased with depth (iii) TEWL increased as more SC layers were removed. Furthermore, areas treated with formulations containing niacinamide were significantly different to pre-treatment baseline and untreated/vehicle-control treated sites, with larger and more mature corneocytes, decreased inflammatory activity, decreased TEWL and increased SC thickness. These data (a) confirm the utility of measures and metrics developed previously for the non-invasive assay of SC barrier function, (b) present an holistic picture of a SC compartment managing barrier function through dynamic optimisation of pathlength and quality of building materials used, and (c) shed new light on niacinamide as a topical formulation adjunct with unique SC barrier-augmentation properties.
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
authors.forename: D
authors.initials: D
authors.lastname: Mohammed
authors.forename: J M
authors.initials: JM
authors.lastname: Crowther
authors.forename: P J
authors.initials: PJ
authors.lastname: Matts
authors.forename: J
authors.initials: J
authors.lastname: Hadgraft
authors.forename: M E
authors.initials: ME
authors.lastname: Lane
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007610:Kallikreins / Q000378:metabolism; D008297:Male; D009536:Niacinamide / Q000008:administration & dosage / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013059:Spectrum Analysis, Raman / Q000379:methods*; D053802:Tryptases / Q000378:metabolism; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000494:pharmacology*; D014870:Water Loss, Insensible / Q000187:drug effects; D055815:Young Adult
chemical_list: D014803:Vitamin B Complex; D009536:Niacinamide; C400147:KLK5 protein, human; C082472:KLK7 protein, human; D007610:Kallikreins; D053802:Tryptases; D005341:Fibrinolysin