Lipid and ultrastructural characterization of reconstructed skin models

Ponec, Maria; Boelsma, Esther; Weerheim, Arij; Mulder, Aat A.; Bouwstra, Joke A.; Mommaas, Mieke

doi:10.1016/s0378-5173(00)00459-2

Cited by 122 publications

(90 citation statements)

References 34 publications

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“…14 For the reconstructed model, the extrusion being retarted, the presence of lamellar bodies is noticed in the uppermost stratum corneum layers. 14,54 The integrated intensity of the band between 780 and 980 cm 21 assigned to polysaccharides CÀ ÀOÀ ÀC stretching vibration 55 seems to be more intense for Episkin, which could originate from the culture medium polysaccharides.…”

Section: Figurementioning

confidence: 96%

Molecular characterization of reconstructed skin model by Raman microspectroscopy: Comparison with excised human skin

et al. 2007

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Human skin is directly exposed to different exogenous agents. Many research works have studied the diffusion, interactions, absorption mechanisms, and/or toxicity of these agents toward different cutaneous structures. With the use of living animals for such tests being more and more rejected; and the number of human volunteers being limited; different types of skin models are used. In the last few years, reconstructed epidermis from cell cultures has been frequently employed, and recent changes in the European chemical policy have approved and encouraged the use of these reconstructed models for skin‐related research works and assessments. Among the techniques used actually to study the skin, Raman microspectroscopy is a rising and powerful nondestructive technique that detects characteristic molecular vibrations. In this study, we created a spectral database to index the vibration peaks and bands of a well‐known reconstructed epidermis model, the Episkin®. The comparison with a native epidermis signal enabled us to put in evidence several spectral differences associated with molecular and structural differences between the skin and the reconstructed model, both maintained in living conditions. In addition to that, we have showed the feasibility of tracking the penetration of a pharmaceutical molecule through the Episkin model. © 2007 Wiley Periodicals, Inc. Biopolymers 87: 261–274, 2007.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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Section: Figurementioning

confidence: 96%

Molecular characterization of reconstructed skin model by Raman microspectroscopy: Comparison with excised human skin

et al. 2007

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“…For these reasons, reconstructed human skin models (RSMs) derived from cell cultures have recently been developed and are increasingly commercially available as in vitro alternatives to animal testing (4)(5)(6)(7)(8)(9). Typical structures of such models are described in more detail in Data S1.…”

Section: Introductionmentioning

confidence: 99%

Comparison of structure and organization of cutaneous lipids in a reconstructed skin model and human skin: spectroscopic imaging and chromatographic profiling

Tfayli

Bonnier²,

Farhane

et al. 2014

Experimental Dermatology

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The use of animals for scientific research is increasingly restricted by legislation, increasing the demand for human skin models. These constructs present comparable bulk lipid content to human skin. However, their permeability is significantly higher, limiting their applicability as models of barrier function, although the molecular origins of this reduced barrier function remain unclear. This study analyses the stratum corneum (SC) of one such commercially available reconstructed skin model (RSM) compared with human SC by spectroscopic imaging and chromatographic profiling. Total lipid composition was compared by chromatographic analysis (HPLC). Raman spectroscopy was used to evaluate the conformational order, lateral packing and distribution of lipids in the surface and skin/RSM sections. Although HPLC indicates that all SC lipid classes are present, significant differences are observed in ceramide profiles. Raman imaging demonstrated that the RSM lipids are distributed in a non-continuous matrix, providing a better understanding of the limited barrier function.

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“…Ultra-structure and lipid composition of Episkin ® , EpiDerm TM and SkinEthic ® was investigated. 21) Skin structure of them was similar to human skin and, however, lipid composition was slightly different with human skin. The growth conditions of CHE influenced the SC barrier functions.…”

Section: Resultsmentioning

confidence: 82%

Prediction of Percutaneous Absorption in Human Using Three-Dimensional Human Cultured Epidermis LabCyte EPI-MODEL

Hikima

Kaneda

Matsuo

et al. 2012

Biological & Pharmaceutical Bulletin

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The objective of this study is to establish a relationship of the skin penetration parameters between the three-dimensional cultured human epidermis LabCyte EPI-MODEL (LabCyte) and hairless mouse (HLM) skin penetration in vitro and to predict the skin penetration and plasma concentration profile in human. The skin penetration experiments through LabCyte and HLM skin were investigated using 19 drugs that have a different molecular weight and lipophilicity. The penetration flux for LabCyte reached 30 times larger at maximum than that for HLM skin. The human data can be estimated from the in silico approach with the diffusion coefficient (D), the partition coefficient (K) and the skin surface concentration (C) of drugs by assuming the bi-layer skin model for both LabCyte and HLM skin. The human skin penetration of β-estradiol, prednisolone, testosterone and ethynylestradiol was well agreed between the simulated profiles and in vitro experimental data. Plasma concentration profiles of β-estradiol in human were also simulated and well agreed with the clinical data. The present alternative method may decrease human or animal skin experiment for in vitro skin penetration.Key words in silico correlation; reconstructed epidermis; LabCyte EPI-MODEL; hairless mouse Human skin permeability of drugs in vivo can be estimated from in vitro experiment using human skin. However, some researchers have ethical and cultural difficulty to get human skins. Thus, animal skins have been widely used for pharmaceutical, toxicological and cosmetic R&D although the skins have a species difference between human. Recently, the 7th Amendment of the EC Cosmetic Directive prohibits the sale of cosmetics and ingredients validated their safety by animal testing with an alternative method. 1) Thus, researchers utilize reconstructed human skin instead of animal skin. The experiments used reconstructed epidermis is approved by the European Centre for the Validation of Alternative Methods (ECVAM) as the scientifically validated methods for skin corrosion and irritation. 2,3) Permeability studies with Episkin ® , EpiDerm TM and SkinEthic ® comparison to human and animal skin were investigated and the authors reported that the penetration flux through the reconstructed skin was higher than that of skin. [4][5][6] The OECD regulations accepted the results from the reconstructed skin 7) but don't approve it as an alternative method for in vitro human skin penetration experiment yet.Skin penetration is widely expressed by the mathematical models on the basis of the process of diffusion and dissolution. Penetration parameters, diffusion coefficient D [cm 2 /s] and partition coefficient K [-], through stratum corneum (SC) and viable skin (VS) of hairless mouse skin are found to well agree with that of human skin. 8) Not only the skin penetration profile but the blood concentration profile in human is well simulated using the penetration parameters determined from hairless mouse skin, the thickness of human SC and VS, the skin enzymatic parameters (first-ord...

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Lipid and ultrastructural characterization of reconstructed skin models

Cited by 122 publications

References 34 publications

Molecular characterization of reconstructed skin model by Raman microspectroscopy: Comparison with excised human skin

Molecular characterization of reconstructed skin model by Raman microspectroscopy: Comparison with excised human skin

Comparison of structure and organization of cutaneous lipids in a reconstructed skin model and human skin: spectroscopic imaging and chromatographic profiling

Prediction of Percutaneous Absorption in Human Using Three-Dimensional Human Cultured Epidermis LabCyte EPI-MODEL

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