title: Modulation of transepithelial electric resistance (TEER) in reconstructed human epidermis by excipients known to permeate intestinal tight junctions.
abstract: Several excipients are commonly used to enhance the drug absorption through simple epithelia of the digestive tract. They permeate the paracellular barrier constituted by tight junctions (TJs). We compared the effects of two excipients, sodium caprate (C10) and a self-emulsifying excipient Labrasol composed of a mixture of caprylocaproyl polyoxyl-8 glycerides, both applied to emerged reconstructed human epidermis either 'systemically', that is by addition to the culture medium, or topically. During the 'systemic' application, which produced cytoplasmic translocation of occludin and leakage of the biotin marker into the lower stratum corneum, the decrease in the trans-epithelial electrical resistance (TEER) was less abrupt with Labrasol when compared with C10, even though both excipients produced comparable final effects over time. With topical Labrasol, a significant TEER decrease was obtained with 5 times the 'systemic' concentrations. Topical application of C10 also resulted in the loss of the barrier function measured with TEER but had dramatic deleterious effects on the tissue morphology observed with light and electron microscopy. Our study demonstrates the potential value of Labrasol as an enhancer of bioavailability of molecules applied through the transcutaneous route. Our results suggest modulation of the epidermal TJs by both compounds. Even though the C10 action was at least partly due to overall cell damage and despite the fact that the decrease in TEER after topical application was apparently related to the permeabilization of the primary barrier of the stratum corneum in the first place.
authors.affiliation: Fundamental, clinical and therapeutic aspects of the skin barrier function, Université Lyon 1, Lyon, France.
authors.forename: Rawad
authors.initials: R
authors.lastname: Abdayem
authors.affiliation: Fundamental, clinical and therapeutic aspects of the skin barrier function, Université Lyon 1, Lyon, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Callejon
authors.affiliation: Gattefossé SAS, Saint-Priest, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Portes
authors.affiliation: Fundamental, clinical and therapeutic aspects of the skin barrier function, Université Lyon 1, Lyon, France.
authors.forename: Plamen
authors.initials: P
authors.lastname: Kirilov
authors.affiliation: Gattefossé SAS, Saint-Priest, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Demarne
authors.affiliation: Fundamental, clinical and therapeutic aspects of the skin barrier function, Université Lyon 1, Lyon, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Pirot
authors.affiliation: Gattefossé SAS, Saint-Priest, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Jannin
authors.affiliation: Fundamental, clinical and therapeutic aspects of the skin barrier function, Université Lyon 1, Lyon, France.
authors.forename: Marek
authors.initials: M
authors.lastname: Haftek
mesh_terms: D000279:Administration, Cutaneous; D001710:Biotin / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003652:Decanoic Acids / Q000494:pharmacology*; D017097:Electric Impedance; D004817:Epidermis / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D005079:Excipients / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes; D062793:Occludin / Q000378:metabolism; D012879:Skin Physiological Phenomena / Q000187:drug effects; D019108:Tight Junctions / Q000187:drug effects; D046509:Tissue Culture Techniques
chemical_list: D003652:Decanoic Acids; D005079:Excipients; D005989:Glycerides; D062793:Occludin; C440220:Labrasol; C031071:decanoic acid; D001710:Biotin
keywords: epidermal barrier; stratum corneum; tight junction; trans-epithelial electrical resistance (TEER); transcutaneous penetration enhancer