title: Measuring the effects of topical moisturizers on changes in stratum corneum thickness, water gradients and hydration in vivo.
abstract: BACKGROUND
  Moisturizers are the most commonly used topically applied product for the treatment of dry skin conditions. They affect many properties and functions of the stratum corneum but some moisturizers have been reported to be detrimental to barrier function. Stratum corneum barrier function is a composite of its total structure and thickness but few studies have taken this into account. As a biosensor, the stratum corneum (SC) will change its structure in response to treatment and a swelling effect has been clearly demonstrated by skin hydration. Recently several moisturizing agents have been shown to have an effect on SC swelling behaviour with conflicting results. However, there is a paucity of data reported for measuring the effects of long-term usage of moisturizers on SC thickness in vivo as, until recently, traditional techniques did not have the resolution to measure the effects of moisturizers on nonpalmoplantar body sites. The development of confocal Raman spectroscopy for use in human subjects provides noninvasive, real-time, in vivo measurement of SC water concentration profiles and we have also used this state of the art equipment to measure the effect of the long-term use of moisturizers on SC thickness for the first time.
  
  
  OBJECTIVE
  To validate the use of confocal Raman spectroscopy (CRS) to measure SC thickness and then use it to investigate the short- and long-term effects of moisturizers (one of which is known to improve SC barrier function) on SC thickness, water gradients and hydration.
  
  
  METHODS
  Two studies were conducted: (i) to validate the use of CRS for measuring SC thickness through comparison with optical coherence tomography (OCT); and (ii) once validated to use CRS to measure the long-term effects of three commercially available moisturizers (A, B, C) on SC thickness and water gradients, together with total hydration, over a 3-week period (2 weeks of treatment and 1 week regression) and compare the spectroscopy-derived hydration value with instrumentally derived capacitance hydration values.
  
  
  RESULTS
  (i) A strong, positive correlation in SC thickness was obtained between CRS and OCT (OCT-derived thickness = 0.96 x CRS-derived thickness, r(2) = 0.93; P <0.0001). OCT was shown, however, to have a lower resolution than CRS in distinguishing SC thickness on thinner nonpalmoplantar body sites. Using the CRS method, differences in SC thickness were readily apparent on different body sites (cheek 12.8 +/- 0.9 microm, volar forearm 18.0 +/- 3.9 microm, leg 22.0 +/- 6.9 microm). (ii) Examining the effects of moisturizers in a blinded, randomized 3-week study in human volunteers (n = 14) demonstrated that only one commercially available formulation (A) changed SC water gradients, thickness and hydration as measured by CRS. These hydration data did not directly correlate with capacitance hydration values.
  
  
  CONCLUSIONS
  (i) In vivo CRS was validated as a technique to measure SC thickness on both palmoplantar and, particularly, on nonpalmoplantar skin sites. (ii) Moisturizers improve skin moisturization but in this study only formulation A improved SC thickness, water gradients and hydration as measured by CRS. We hypothesize that this was due to compositional differences between the products. We believe that niacinamide (nicotinamide, vitamin B(3)) is probably contributing significantly to this effect, as it has been proven to increase epidermal lipogenesis and SC barrier function in other studies. These results show that by using CRS, we were able for the first time to determine the effect of moisturizer on multiple SC barrier endpoints including SC thickness, and water content as a function of depth and total SC water content.
authors.affiliation: Procter & Gamble Technical Centres Ltd., Rusham Park, Whitehall Lane, Egham, Surrey, TW20 9NW, UK. crowther.j.1@pg.com
authors.forename: J M
authors.initials: JM
authors.lastname: Crowther
authors.forename: A
authors.initials: A
authors.lastname: Sieg
authors.forename: P
authors.initials: P
authors.lastname: Blenkiron
authors.forename: C
authors.initials: C
authors.lastname: Marcott
authors.forename: P J
authors.initials: PJ
authors.lastname: Matts
authors.forename: J R
authors.initials: JR
authors.lastname: Kaczvinsky
authors.forename: A V
authors.initials: AV
authors.lastname: Rawlings
mesh_terms: D000287:Administration, Topical; D000328:Adult; D019540:Area Under Curve; D001834:Body Water / Q000187:drug effects / Q000502:physiology; D004643:Emollients / Q000008:administration & dosage* / Q000494:pharmacology; D004817:Epidermis / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005542:Forearm; D006801:Humans; D016014:Linear Models; D008297:Male; D018613:Microscopy, Confocal / Q000295:instrumentation / Q000379:methods*; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000494:pharmacology; D012016:Reference Values; D012869:Skin Absorption / Q000187:drug effects; D013059:Spectrum Analysis, Raman / Q000295:instrumentation / Q000379:methods*; D041623:Tomography, Optical Coherence / Q000379:methods
chemical_list: D004643:Emollients; D009536:Niacinamide