Structure and function of the stratum corneum permeability barrier
Abstract
The main function of the epidermis is to generate an impermeable outer layer, the stratum corneum. The stratum corneum can be considered morphologically and functionally to represent a two‐compartment system composed of: (1) anucleate corneocytes (the bricks), largely composed of fibrous protein networks; and (2) the intercellular matrix (the mortar), predominantly composed of neutral lipid. Whereas much prior and current work on the stratum corneum has focused on the protein biochemistry leading to the formation of the keratinized corneocyte (“keratinization”), this paper is concerned with the formation, composition, and function of the intercellular matrix of the stratum corneum. For those interested in permeability barrier function, percutaneous transport, and the cutaneous reservoir, as well as most inherited disorders of cornification, it is critical to understand the “mortar,” for it is this domain that logically regulates all of these important phenomena.
Number of times cited: 62
- Ahmad Shakeel, Francesca R. Lupi, Domenico Gabriele, Noemi Baldino and Bruno De Cindio, Bigels: A unique class of materials for drug delivery applications, Soft Materials, (1), (2018).
- Sara Al-Marabeh, Enam Khalil, Mohammad Khanfar, Amal G. Al-Bakri and Muhammed Alzweiri, A prodrug approach to enhance azelaic acid percutaneous availability, Pharmaceutical Development and Technology, 22, 4, (578), (2017).
- Katja Bäsler and Johanna M. Brandner, Tight junctions in skin inflammation, Pflügers Archiv - European Journal of Physiology, 469, 1, (3), (2017).
- Yan Cao, Prateek Kakar, Md. Nazir Hossen, Mei X. Wu and Xinyuan Chen, Sustained epidermal powder drug delivery via skin microchannels, Journal of Controlled Release, 10.1016/j.jconrel.2017.01.030, 249, (94-102), (2017).
- Yelena Pyatski, Qihong Zhang, Richard Mendelsohn and Carol R. Flach, Effects of permeation enhancers on flufenamic acid delivery in Ex vivo human skin by confocal Raman microscopy, International Journal of Pharmaceutics, 10.1016/j.ijpharm.2016.04.011, 505, 1-2, (319-328), (2016).
- Tasnuva Haque, Khondaker M. Rahman, David E. Thurston, Jonathan Hadgraft and Majella E. Lane, Topical therapies for skin cancer and actinic keratosis, European Journal of Pharmaceutical Sciences, 10.1016/j.ejps.2015.06.013, 77, (279-289), (2015).
- Gary P.J. Moss, Introduction, Novel Delivery Systems for Transdermal and Intradermal Drug Delivery, (1-40), (2015).
- Canan Dagdeviren, Yan Shi, Pauline Joe, Roozbeh Ghaffari, Guive Balooch, Karan Usgaonkar, Onur Gur, Phat L. Tran, Jessi R. Crosby, Marcin Meyer, Yewang Su, R. Chad Webb, Andrew S. Tedesco, Marvin J. Slepian, Yonggang Huang and John A. Rogers, Conformal piezoelectric systems for clinical and experimental characterization of soft tissue biomechanics, Nature Materials, 14, 7, (728), (2015).
- Santosh Bashyal and Sangkil Lee, Delivery of biopharmaceuticals using combination of liposome and iontophoresis: a review, Journal of Pharmaceutical Investigation, 45, 7, (611), (2015).
- K. Ishida, Y. Obata, C. Akagi, Y. Onuki and K. Takayama, Practical syntheses of D-erythro and L-threo-ceramide [NDS] and difference in contribution of each isomer in microstructure of stratum corneum intercellular lipids, Journal of Drug Delivery Science and Technology, 24, 6, (689), (2014).
- L Kilpatrick-Liverman, J Mattai, R Tinsley and Q Wu, Mechanisms of Skin Hydration, Handbook of Cosmetic Science and Technology, Fourth Edition, 10.1201/b16716-8, (81-92), (2014).
- Masaki Ujihara, Response for External Stimulation on the Skin, Skin Bioscience, 10.1201/b16476-3, (43-81), (2014).
- Khurram Rehman and Mohd Hanif Zulfakar, Recent advances in gel technologies for topical and transdermal drug delivery, Drug Development and Industrial Pharmacy, 10.3109/03639045.2013.828219, 40, 4, (433-440), (2013).
- Annett Schroeter, Tanja Engelbrecht and Reinhard H. H. Neubert, Influence of short chain ceramides and lipophilic penetration enhancers on the nano-structure of stratum corneum model membranes studied using neutron diffraction, Frontiers of Chemical Science and Engineering, 7, 1, (29), (2013).
- Johannes M. Nitsche and Gerald B. Kasting, A Microscopic Multiphase Diffusion Model of Viable Epidermis Permeability, Biophysical Journal, 104, 10, (2307), (2013).
- Zhongni Wang, Jing Zhao, Wu Zhou, Xilian Wei and Xiaolu Tang, Lamellar Liquid Crystals Formed in Ternary DEP/Oil/Water Systems, Journal of Dispersion Science and Technology, 34, 4, (546), (2013).
- John P. Sundberg, Christopher S. Potter and Lloyd E. King, Skin and Adnexa of the Laboratory Mouse, The Laboratory Mouse, 10.1016/B978-0-12-382008-2.00009-X, (193-208), (2012).
- Russel M. Walters, Guangru Mao, Euen T. Gunn and Sidney Hornby, Cleansing Formulations That Respect Skin Barrier Integrity, Dermatology Research and Practice, 2012, (1), (2012).
- G. Mao, C. R. Flach, R. Mendelsohn and R. M. Walters, Imaging the Distribution of Sodium Dodecyl Sulfate in Skin by Confocal Raman and Infrared Microspectroscopy, Pharmaceutical Research, 10.1007/s11095-012-0748-y, 29, 8, (2189-2201), (2012).
- Josef Jampilek and Katerina Brychtova, Azone analogues: classification, design, and transdermal penetration principles, Medicinal Research Reviews, 32, 5, (907-947), (2010).
- Ajay Banga, Percutaneous Absorption and Enhancement Strategies, Transdermal and Intradermal Delivery of Therapeutic Agents, 10.1201/b10906-2, (1-26), (2011).
- Zoe Diana Draelos, Troubleshooting problematic ingredients, Cosmetics and Dermatological Problems and Solutions: A Problem Based Approach, 10.3109/9781841847412.015, (103-111), (2011).
- Thomas Schmidts, Dorota Dobler, Sylvia von den Hoff, Peggy Schlupp, Holger Garn and Frank Runkel, Protective effect of drug delivery systems against the enzymatic degradation of dermally applied DNAzyme, International Journal of Pharmaceutics, 10.1016/j.ijpharm.2011.03.023, 410, 1-2, (75-82), (2011).
- Cornelia Laule, Sumia Tahir, Charmaine L. L. Chia, Irene M. Vavasour, Neil Kitson and Alex L. MacKay, A proton NMR study on the hydration of normal versus psoriatic stratum corneum: linking distinguishable reservoirs to anatomical structures, NMR in Biomedicine, 23, 10, (1181-1190), (2010).
- L Kilpatrick-Liverman, J Mattai, R Tinsley and J Wu, Mechanisms of Skin Hydration, Handbook of Cosmetic Science and Technology, Third Edition, 10.1201/b15273-10, (91-106), (2013).
- Paul A. McCarron, Ryan F. Donnelly and A. David Woolfson, Autoradiographic and Scintillation Analysis of 5-Aminolevulinic Acid Permeation Through Epithelialised Tissue: Implications for Topical Photodynamic Therapy of Superficial Gynaecological Neoplasias, Pharmaceutical Research, 10.1007/s11095-007-9352-y, 25, 4, (812-826), (2007).
- Uwe Pliquett, Ch. Gusbeth and Richard Nuccitelli, A propagating heat wave model of skin electroporation, Journal of Theoretical Biology, 251, 2, (195), (2008).
- Johannes M. Nitsche, Tsuo‐Feng Wang and Gerald B. Kasting, A two‐phase analysis of solute partitioning into the stratum corneum, Journal of Pharmaceutical Sciences, 95, 3, (649-666), (2006).
- Katja Lahm and Geoffrey Lee, Penetration of crystalline powder particles into excised human skin membranes and model gels from a supersonic powder injector, Journal of Pharmaceutical Sciences, 95, 7, (1511-1526), (2006).
- U. Pliquett, S. Gallo, S.W. Hui, Ch. Gusbeth and E. Neumann, Local and transient structural changes in stratum corneum at high electric fields: Contribution of Joule heating, Bioelectrochemistry, 67, 1, (37), (2005).
- John D. Walker, Ingrid Gerner, Etje Hulzebos and Kerstin Schlegel, (Q)SARs for Predicting Skin Irritation and Corrosion: Mechanisms, Transparency and Applicability of Predictions, QSAR & Combinatorial Science, 23, 9, (721-725), (2004).
- John P Sundberg, Skin and Adnexa of the Laboratory Mouse, The Laboratory Mouse, 10.1016/B978-012336425-8/50065-0, (195-206), (2004).
- J.R. Hill and P.W. Wertz, Molecular models of the intercellular lipid lamellae from epidermal stratum corneum, Biochimica et Biophysica Acta (BBA) - Biomembranes, 1616, 2, (121), (2003).
- Uwe F. Pliquett, Gregory T. Martin and James C. Weaver, Kinetics of the temperature rise within human stratum corneum during electroporation and pulsed high-voltage iontophoresis, Bioelectrochemistry, 57, 1, (65), (2002).
- Günther Schneider, Sven Gohla, Jörg Schreiber, Waltraud Kaden, Uwe Schönrock, Hartmut Schmidt‐Lewerkühne, Annegret Kuschel, Xenia Petsitis, Wolfgang Pape, Hellmut Ippen and Walter Diembeck, Skin Cosmetics, Ullmann's Encyclopedia of Industrial Chemistry, (2001).
- Antonio Alonso, Nilce C Meirelles and Marcel Tabak, Lipid chain dynamics in stratum corneum studied by spin label electron paramagnetic resonance, Chemistry and Physics of Lipids, 104, 2, (101), (2000).
- Uwe F Pliquett, Christian A Gusbeth and James C Weaver, Non-linearity of molecular transport through human skin due to electric stimulus, Journal of Controlled Release, 68, 3, (373), (2000).
- Chandrasekharan Ramachandran and David Fleisher, Transdermal delivery of drugs for the treatment of bone diseases, Advanced Drug Delivery Reviews, 10.1016/S0169-409X(00)00062-4, 42, 3, (197-223), (2000).
- Antonio Alonso, Judes Gonçalves dos Santos and Marcel Tabak, Stratum corneum protein mobility as evaluated by a spin label maleimide derivative, Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1478, 1, (89), (2000).
- Rong Guo, Jun Yang, Stig E. Friberg, Victor Landeryou and Larry Hall, POLYGLYCERYL OLEATE SURFACTANTS AND THE STRATUM CORNEUM LIPID, Journal of Dispersion Science and Technology, 21, 1, (1), (2000).
- Neti Waranuch, Chandrasekharan Ramachandran and Norman D. Weiner, Controlled Topical Delivery of Hydrocortisone and Mannitol Via Select Pathways, Journal of Liposome Research, 9, 1, (139), (1999).
- Sun Gyoo Park, Young Deuk Kim, Jin Jun Kim and Seh Hoon Kang, Two possible classifications of facial skin type by two parameters in Korean women: sebum excretion rate (SER) and skin surface relief (SSR), Skin Research and Technology, 5, 3, (189-194), (2006).
- Uwe Pliquett, Mechanistic studies of molecular transdermal transport due to skin electroporation, Advanced Drug Delivery Reviews, 35, 1, (41), (1999).
- Jerel Palenske and Vera B. Morhenn, Changes in the Skin's Capacitance after Damage to the Stratum Corneum in Humans, Journal of Cutaneous Medicine and Surgery, 3, 3, (127), (1999).
- C.C. Müller-Goymann and U. Alberg, Modified water containing hydrophilic ointment with suspended hydrocortisone-21-acetate – the influence of the microstructure of the cream on the in vitro drug release and in vitro percutaneous penetration, European Journal of Pharmaceutics and Biopharmaceutics, 47, 2, (139), (1999).
- Gil Yosipovitch, Glen L. Xiong, Erhard Haus, Linda Sackett-Lundeen, Israel Ashkenazi and Howard I. Maibach, Time-Dependent Variations of the Skin Barrier Function in Humans: Transepidermal Water Loss, Stratum Corneum Hydration, Skin Surface pH, and Skin Temperature, Journal of Investigative Dermatology, 110, 1, (20), (1998).
- A. Saïd, S. Makki, P. Muret, Ph. Humbert and J. Millet, Psoralens percutaneous permeation across the human whole skin and the epidermis in respect to their polarity (in vitro study), Journal of Dermatological Science, 14, 2, (136), (1997).
- Antonio Alonso, Nilce C. Meirelles, Victor E. Yushmanov and Marcel Tabak, Water Increases the Fluidity of Intercellular Membranes of Stratum Corneum: Correlation with Water Permeability, Elastic, and Electrical Resistance Properties, Journal of Investigative Dermatology, 106, 5, (1058), (1996).
- Lucio Andreassi, Bioengineering in dermatology: General aspects and perspectives, Clinics in Dermatology, 13, 4, (289), (1995).
- Samir Mitragotri, David A. Edwards, Daniel Blankschtein and Robert Langer, A mechanistic study of ultrasonically‐enhanced transdermal drug delivery, Journal of Pharmaceutical Sciences, 84, 6, (697-706), (2006).
- Lutz Hegemann, Christa Forstinger, Bernhard Partsch, Irmgard Lagler, Sabine Krotz and Klaus Wolff, Microdialysis in Cutaneous Pharmacology: Kinetic Analysis of Transdermally Delivered Nicotine, Journal of Investigative Dermatology, 104, 5, (839), (1995).
- Stig E. Friberg, Amphiphilic Association Structure and Skin Lotions, Journal of Dispersion Science and Technology, 15, 3, (359), (1994).
- David A. Edwards and Robert Langer, A Linear Theory of Transdermal Transport Phenomena, Journal of Pharmaceutical Sciences, 83, 9, (1315), (1994).
- Stefania Motta, Marcello Monti, Silvia Sesana, Ruggero Caputo, Stephana Carelli and Riccardo Ghidoni, Ceramide composition of the psoriatic scale, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1182, 2, (147), (1993).
- Stig E. Friberg and Zhu-ning Ma, PARTITION OF FREE AMINO ACIDS BETWEEN STRATUM CORNEUM MODEL LIPIDS AND CORNEOCYTES, Journal of Dispersion Science and Technology, 14, 4, (481), (1993).
- D.T. Parrott and J.E. Turner, Mesophase formation by ceramides and cholesterol: a model for stratum corneum lipid packing?, Biochimica et Biophysica Acta (BBA) - Biomembranes, 1147, 2, (273), (1993).
- R. Gay, M. Swiderek, D. Nelson and A. Ernesti, The living skin equivalent as a model in vitro for ranking the toxic potential of dermal irritants, Toxicology in Vitro, 6, 4, (303), (1992).
- Lutz W. D. Weber, Achim Zesch and Karl Rozman, Decontamination of Human Skin Exposed to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) in Vitro, Archives of Environmental Health: An International Journal, 47, 4, (302), (1992).
- Lutz W. D. Weber, Achim Zesch and Karl Rozman, Penetration, distribution and kinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin in human skin in vitro, Archives of Toxicology, 65, 5, (421), (1991).
- Harry E Boddé, Bert Holman, Ferry Spies, Arij Weerheim, Johanna Kempenaar, Mieke Mommaas and Maria Ponec, Freeze-Fracture Electron Microscopy of In Vitro Reconstructed Human Epidermis, Journal of Investigative Dermatology, 95, 1, (108), (1990).
- Walter Magerl, Rod A. Westerman, Bernd Möhner and Hermann O. Handwerker, Properties of Transdermal Histamine Iontophoresis: Differential Effects of Season, Gender, and Body Region, Journal of Investigative Dermatology, 94, 3, (347), (1990).
- X.H. Zhou and A. Li Wan Po, Comparison of enzymic activities of tissues lining portals of drug absorption, using the rat as a model, International Journal of Pharmaceutics, 62, 2-3, (259), (1990).




