title: Permeability and lipid organization of a novel psoriasis stratum corneum substitute.
abstract: Lipids in the uppermost layer of the skin, the stratum corneum (SC), play an important role in the skin barrier properties. The main lipid classes are ceramides, cholesterol and free fatty acids. In previous studies a stratum corneum substitute (SCS) was developed, solely prepared from the SC lipids. The SCS mimics the lipid barrier properties of SC very closely. The present study aimed to design a psoriasis SCS (PS-SCS) mimicking several aspects of the lipid composition in SC from psoriasis patients. This PS-SCS showed a different lipid organization than SCS. The main differences were a reduced presence of an orthorhombic packing and an increased level of crystalline cholesterol. These changes resulted in lower flux of hydrocortisone across PS-SCS than across SCS and SC, which was most likely attributed to the higher level of phase separated crystalline cholesterol in PS-SCS. As propylene glycol (PG) is often used in dermatological formulations, in subsequent studies the interaction of PG with SC and SCS membranes was also investigated. These studies revealed that PG increased the permeability of hydrocortisone, mainly by selectively extracting cholesterol from SCS membranes and SC. This may play an important role in the penetration enhancing effect of PG.
authors.affiliation: LEO Pharma, Department of DMPK and Safety, Industriparken 55, 2750 Ballerup, Denmark; Leiden/Amsterdam Center for Drug Research (LACDR), Department of Drug Delivery Technology, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands. Electronic address: line.basse@leo-pharma.com.
authors.forename: Line Hollesen
authors.initials: LH
authors.lastname: Basse
authors.forename: Daniël
authors.initials: D
authors.lastname: Groen
authors.forename: Joke A
authors.initials: JA
authors.lastname: Bouwstra
mesh_terms: D002518:Ceramides / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D004817:Epidermis / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000737:chemistry; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D010539:Permeability; D019946:Propylene Glycol / Q000737:chemistry; D011565:Psoriasis / Q000378:metabolism*; D017768:Skin, Artificial
chemical_list: D002518:Ceramides; D005230:Fatty Acids, Nonesterified; D008563:Membrane Lipids; D019946:Propylene Glycol; D002784:Cholesterol; D006854:Hydrocortisone
keywords: 6-hydroxysphingosine; A; Barrier function; CER; CHOL; Dermal drug delivery; Diseased skin; EO; FFA; FTIR; Fourier transform infrared spectroscopy; H; LPP; N; P; PG; PS-SCS; Propylene glycol; S; SAXD; SCS; SPP; Skin; Stratum corneum lipids; ceramides; cholesterol; dS; dihydroxysphingosine; free fatty acids; long periodicity phase; non-hydroxy; phytosphingosine; propylene glycol; psoriasis stratum corneum substitute; short periodicity phase; small angle X-ray diffraction; sphingosine; stratum corneum substitute; α-hydroxy; ω-hydroxy