title: Increased cutaneous absorption reflects impaired barrier function of reconstructed skin models mimicking keratinisation disorders.
abstract: The aim of this study was to assess a recently established 3D model of congenital ichthyosis, representing severe epidermal barrier function defects, for skin penetration and permeation. We have generated disease models by knock-down of either TGM1 or ALOXE3 in primary human keratinocytes, and using keratinocytes and fibroblasts from patients with congenital ichthyosis. The results indicate disturbed barrier function as demonstrated by increased permeation of testosterone and caffeine particularly in TGM1 knock-down models compared to control models. In addition, enhanced penetration of the model dye nile red incorporated into solid lipid nanoparticles and core-multishell nanotransporters, respectively, was evident in disease models. Thus, in vitro skin disease models reproduce differences in barrier permeability and function seen in congenital ichthyosis and pave the way to personalised disease models. Furthermore, our findings indicate that nanocarriers may be useful in new, topical therapeutic approaches for the currently very limited treatment of congenital ichthyosis.
authors.affiliation: Dermatogenetics, Division of Human Genetics and Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria; Dermatogenetics, Cologne Center for Genomics, University of Cologne, Cologne, Germany.
authors.forename: Katja-Martina
authors.initials: KM
authors.lastname: Eckl
authors.forename: Günther
authors.initials: G
authors.lastname: Weindl
authors.forename: Katharina
authors.initials: K
authors.lastname: Ackermann
authors.forename: Sarah
authors.initials: S
authors.lastname: Küchler
authors.forename: Ramona
authors.initials: R
authors.lastname: Casper
authors.forename: Michał R
authors.initials: MR
authors.lastname: Radowski
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Hennies
authors.forename: Monika
authors.initials: M
authors.lastname: Schäfer-Korting
mesh_terms: D016475:3T3 Cells; D000368:Aged; D000818:Animals; D002648:Child; D005347:Fibroblasts; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000378:metabolism*; D015603:Keratinocytes; D008297:Male; D051379:Mice; D012869:Skin Absorption; D023822:Tissue Engineering
keywords: epidermal barrier; keratinization disorder; nanoparticles; skin disease models; skin permeation and penetration