title: Studying the effectiveness of penetration enhancers to deliver retinol through the stratum cornum by in vivo confocal Raman spectroscopy.
abstract: The purpose of this study is to monitor in vivo the effect of chemical penetration enhancers on the delivery of trans-retinol into human skin. Chemical penetration enhancers reversibly alter barrier properties of the SC by disruption of the membrane structures or maximising drug solubility with the skin. So far, most of permeation or penetration experiments are performed in vitro. Raman spectroscopy is uniquely placed to be able to measure biological processes in vivo and this paper shows for the first time that the effect of penetration enhancer on the delivery of trans-retinol can successfully be measured in vivo using this technique. Here, the volar forearm of volunteers was treated with four formulations. One formulation is a highly effective model delivery system identified from ex vivo experiments: trans-retinol in Propylene Glycol (PG)/ethanol, with PG being a well-known and efficient penetration enhancer. The other three formulations are based on 0.3% trans-retinol in Caprylic/Capric Acid Triglyceride (MYRITOL 318), an oil commonly used in skin creams but in two of them a specific penetration enhancer is added. One contains a lipid extractor, Triton X 100, whereas another formulation contains a lipid fluidiser, Oleic Acid. Solutions were applied once and measurements were performed up to 6 h after treatment. Remarkable differences in the delivery of trans-retinol between formulation with or without penetration enhancer can clearly be seen. Moreover, the type of penetration enhancer is also shown to influence the delivery. While using the Oleic Acid, which is a lipid fluidiser, a better delivery of trans-retinol in the skin can be detected. For the first time, the effect of penetration enhancer on the delivery of trans-retinol has been monitored, non invasively in vivo, with time.
authors.affiliation: Measurement Science Unit and Corporate Research, Unilever R&D, Colworth Science Park, Sharnbrook, Bedford, MK44 1LQ, United Kingdom.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Mélot
authors.forename: Paul D A
authors.initials: PD
authors.lastname: Pudney
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Williamson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Caspers
authors.forename: Andre
authors.initials: A
authors.lastname: Van Der Pol
authors.forename: Gerwin J
authors.initials: GJ
authors.lastname: Puppels
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017830:Octoxynol / Q000494:pharmacology*; D019301:Oleic Acid / Q000494:pharmacology*; D019946:Propylene Glycol / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D013059:Spectrum Analysis, Raman / Q000379:methods*; D014801:Vitamin A / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014815:Vitamins / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D014815:Vitamins; D014801:Vitamin A; D019301:Oleic Acid; D019946:Propylene Glycol; D017830:Octoxynol