title: Tight junctions form a barrier in porcine hair follicles.
abstract: Follicular penetration has gained increasing interest regarding (i) safety concerns about (environmentally born) xenobiotics available to the hair follicle (HF), e.g. nanomaterials or allergens which should not enter the skin, and (ii) the possibility for non-invasive follicular drug and antigen delivery. However, not much is known about barriers in the HF which have to be surpassed upon uptake and/or penetration into surrounding tissue. Thus, aim of this work was a detailed investigation of this follicular barrier function, as well as particle uptake into the HF of porcine skin which is often used as a model system for human skin for such purposes. We show that follicular tight junctions (TJs) form a continuous barrier from the infundibulum down to the suprabulbar region, complementary to the stratum corneum in the most exposed upper follicular region, but remaining as the only barrier in the less accessible lower follicular regions. In the bulbar region of the HF no TJ barrier was found, demonstrating the importance of freely supplying this hair-forming part with e.g. nutrients or hormones from the dermal microenvironment. Moreover, the dynamic character of the follicular TJ barrier was shown by modulating its permeability using EDTA. After applying polymeric model-nanoparticles (154 nm) to the skin, transmission electron microscopy revealed that the majority of the particles were localized in the upper part of the HF where the double-barrier is present. Only few penetrated deeper, reaching regions where TJs act as the only barrier, and no particles were observed in the bulbar, barrier-less region. Lastly, the equivalent expression and distribution of TJ proteins in human and porcine HF further supports the suitability of porcine skin as a predictive model to study the follicular penetration and further biological effects of dermally applied nanomaterials in humans.
authors.affiliation: Department of Pharmacy, Saarland University, Campus A4 1, Saarbruecken 66123, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Mathes
authors.affiliation: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf (UKE), Martinistrasse 52, Hamburg 20246, Germany. Electronic address: brandner@uke.de.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Brandner
authors.affiliation: Advanced Light and Electron Microscopy (ZBS 4), Robert-Koch-Institute, Nordufer 20, 13353 Berlin-Wedding, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Laue
authors.affiliation: Department of Drug Delivery, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Center for Infection Research (HZI), Stuhlsatzenhausenweg 85, Saarbruecken 66123, Germany.
authors.forename: Simon S
authors.initials: SS
authors.lastname: Raesch
authors.affiliation: Department of Drug Delivery, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Center for Infection Research (HZI), Stuhlsatzenhausenweg 85, Saarbruecken 66123, Germany.
authors.forename: Steffi
authors.initials: S
authors.lastname: Hansen
authors.affiliation: UKE Microscopy Imaging Facility, University Hospital Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany.
authors.forename: Antonio V
authors.initials: AV
authors.lastname: Failla
authors.affiliation: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf (UKE), Martinistrasse 52, Hamburg 20246, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Vidal
authors.affiliation: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf (UKE), Martinistrasse 52, Hamburg 20246, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Moll
authors.affiliation: Department of Pharmacy, Saarland University, Campus A4 1, Saarbruecken 66123, Germany.
authors.forename: Ulrich F
authors.initials: UF
authors.lastname: Schaefer
authors.affiliation: Department of Pharmacy, Saarland University, Campus A4 1, Saarbruecken 66123, Germany; Department of Drug Delivery, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Center for Infection Research (HZI), Stuhlsatzenhausenweg 85, Saarbruecken 66123, Germany. Electronic address: Claus-Michael.Lehr@helmholtz-hzi.de.
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D000818:Animals; D018859:Hair Follicle / Q000378:metabolism / Q000648:ultrastructure*; D013552:Swine; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure*
keywords: Biotin; Claudin; Microscopy; Nanoparticle; Occludin; Penetration; ZO-1