Skip to main content

Advertisement

SpringerLink
Log in

In Vitro Modeling of Skin Barrier Disruption and its Recovery by Ceramide-Based Formulations

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Disrupted skin barrier, one of the severe attributes of inflammatory skin diseases, is caused by lower content and pathological changes of lipids in the uppermost skin layer—stratum corneum (SC). Restoring skin barrier with native skin lipids, especially ceramides (Cers), appears to be a promising therapy with minimum side effects. For testing the efficiency of these formulations, suitable in vitro models of the skin with disrupted barriers are needed. For the similarity with the human tissue, our models were based on the pig ear skin. Three different ways of skin barrier disruption were tested and compared: tape stripping, lipid extraction with organic solvents, and barrier disruption by sodium lauryl sulfate. The level of barrier disruption was investigated by permeation studies, and parameters of each method were modified to reach significant changes between the non-disrupted skin and our model. Fourier transform infrared (FTIR) spectroscopy was employed to elucidate the changes of the skin permeability on the molecular scale. Further, the potential of the developed models to be restored by skin barrier repairing agents was evaluated by the same techniques. We observed a significant decrease in permeation characteristics through our in vitro models treated with the lipid mixtures compared to the untreated damaged skin, which implied that the skin barrier was substantially restored. Taken together, the results suggest that our in vitro models are suitable for the screening of potential barrier repairing agents.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

AD:

Atopic dermatitis

ATR:

Attenuated total reflectance

BR:

Barrier recovery percent

Cer:

Ceramide

Cer AP:

N-2-hydroxystearoyl phytosphingosine

Cer NP:

N-stearoyl phytosphingosine

Chol:

Cholesterol

CS:

Cholesterol sulfate

DR:

Disrupting ratio

DSC:

Differential scanning calorimetry

FFA:

Free fatty acids

FTIR:

Fourrier transform infrared

IND:

Indomethacin

IR:

Infrared

HPLC:

High-performance liquid chromatography

PBS:

Phosphate buffer saline

SA:

Stearic acid

SC:

Stratum corneum

SCORAD:

Severity scoring of atopic dermatitis

SEM:

Standard error of the mean

SLS:

Sodium lauryl sulfate

TCS:

Topical corticosteroids

TEWL:

Transepidermal water loss

TH:

Theophylline

References

  1. Menon GK. New insights into skin structure: scratching the surface. Adv Drug Del Rev. 2002;54(Supplement):S3–17.

    Article  CAS  Google Scholar 

  2. Fartasch M. The nature of the epidermal barrier: structural aspects. Adv Drug Deliv Rev. 1996;18(3):273–82.

    Article  CAS  Google Scholar 

  3. Menon GK, Cleary GW, Lane ME. The structure and function of the stratum corneum. Int J Pharm. 2012;435(1):3–9.

    Article  CAS  PubMed  Google Scholar 

  4. Yardley HJ, Summerly R. Lipid composition and metabolism in normal and diseased epidermis. Pharmacol Ther. 1981;13(2):357–83.

    Article  CAS  PubMed  Google Scholar 

  5. Schurer NY, Elias PM. The biochemistry and function of stratum corneum lipids. In: Elias PM, editor. Advances in Lipid Research. 24: Elsevier; 1991. p. 27–56.

  6. Lampe MA, Burlingame AL, Whitney J, Williams ML, Brown BE, Roitman E, et al. Human stratum corneum lipids: characterization and regional variations. J Lipid Res. 1983;24(2):120–30.

    Article  CAS  PubMed  Google Scholar 

  7. Feingold KR, Elias PM. Role of lipids in the formation and maintenance of the cutaneous permeability barrier. Biochim Biophys Acta (BBA) - Mol Cell Biol Lipids. 2014;1841(3):280–94.

    CAS  Google Scholar 

  8. Bouwstra JA, Ponec M. The skin barrier in healthy and diseased state. Biochim Biophys Acta, Biomembr. 2006;1758(12):2080–95.

    Article  CAS  Google Scholar 

  9. van Smeden J, Janssens M, Gooris GS, Bouwstra JA. The important role of stratum corneum lipids for the cutaneous barrier function. Biochim Biophys Acta, Mol Cell Biol Lipids. 2014;1841(3):295–313.

    Article  Google Scholar 

  10. Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population–based study. J Allergy Clin Immunol. 2013;132(5):1132–8.

    Article  PubMed  Google Scholar 

  11. Wolf R, Orion E, Ruocco E, Ruocco V. Abnormal epidermal barrier in the pathogenesis of psoriasis. Clin Dermatol. 2012;30(3):323–8.

    Article  PubMed  Google Scholar 

  12. van Smeden J, Bouwstra JA. Stratum corneum lipids: their role for the skin barrier function in healthy subjects and atopic dermatitis patients. Curr Probl Dermatol. 2016;49:8–26.

    Article  PubMed  Google Scholar 

  13. Borodzicz S, Rudnicka L, Mirowska-Guzel D, Cudnoch-Jedrzejewska A. The role of epidermal sphingolipids in dermatologic diseases. Lipids Health Dis. 2016;15(1):13.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Callen J, Chamlin S, Eichenfield LF, Ellis C, Girardi M, Goldfarb M, et al. A systematic review of the safety of topical therapies for atopic dermatitis. Br J Dermatol. 2007;156(2):203–21.

    Article  CAS  PubMed  Google Scholar 

  15. Hengge UR, Ruzicka T, Schwartz RA, Cork MJ. Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol. 2006;54(1):1–15.

    Article  PubMed  Google Scholar 

  16. Arkwright PD, Motala C, Subramanian H, Spergel J, Schneider LC, Wollenberg A. Management of difficult-to-treat atopic dermatitis. J Allergy Clin Immunol Pract. 2013;1(2):142–51.

    Article  PubMed  Google Scholar 

  17. Roekevisch E, Leeflang MMG, Schram ME, Campbell LE, Irwin McLean WH, Kezic S, et al. Patients with atopic dermatitis with filaggrin loss-of-function mutations show good but lower responses to immunosuppressive treatment. Br J Dermatol. 2017;177(6):1745–6.

    Article  CAS  PubMed  Google Scholar 

  18. Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116–32.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Berkers T, Visscher D, Gooris GS, Bouwstra JA. Topically applied ceramides interact with the stratum corneum lipid matrix in compromised ex vivo skin. Pharm Res. 2018;35(3):48.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Chamlin SL, Frieden IJ, Fowler A, Williams M, Kao J, Sheu M, et al. Ceramide-dominant, barrier-repair lipids improve childhood atopic dermatitis. Arch Dermatol. 2001;137(8):1110–2.

    CAS  PubMed  Google Scholar 

  21. Elias PM. Lipid abnormalities and lipid-based repair strategies in atopic dermatitis. Biochim Biophys Acta (BBA) - Mol Cell Biol Lipids. 2014;1841(3):323–30.

    CAS  Google Scholar 

  22. Draelos ZD. New treatments for restoring impaired epidermal barrier permeability: skin barrier repair creams. Clin Dermatol. 2012;30(3):345–8.

    Article  PubMed  Google Scholar 

  23. Sugarman JL, Parish LC. Efficacy of a lipid-based barrier repair formulation in moderate-to-severe pediatric atopic dermatitis. J Drugs Dermatol. 2009;8(12):1106–11.

    PubMed  Google Scholar 

  24. Vovesná A, Zhigunov A, Balouch M, Zbytovská J. Ceramide liposomes for skin barrier recovery: a novel formulation based on natural skin lipids. Int J Pharm. 2021;596:120264.

    Article  PubMed  Google Scholar 

  25. Bashir SJ, Chew A-L, Anigbogu A, Dreher F, Maibach HI. Physical and physiological effects of stratum corneum tape stripping. Skin Res Technol. 2001;7(1):40–8.

    Article  CAS  PubMed  Google Scholar 

  26. Yoshizawa Y, Kitamura K, Kawana S, Maibach HI. Water, salts and skin barrier of normal skin. Skin Res Technol. 2003;9(1):31–3.

    Article  PubMed  Google Scholar 

  27. Man M-Q, Feingold KR, Thornfeldt CR, Elias PM. Optimization of physiological lipid mixtures for barrier repair. J Invest Dermatol. 1996;106(5):1096–101.

    Article  Google Scholar 

  28. Bissonnette R, Maari C, Provost N, Bolduc C, Nigen S, Rougier A, et al. A double-blind study of tolerance and efficacy of a new urea-containing moisturizer in patients with atopic dermatitis. J Cosmet Dermatol. 2010;9(1):16–21.

    Article  PubMed  Google Scholar 

  29. Seghers AC, Cai SC, Ho MSL, Giam YC, Tan L, Grönhagen CM, et al. Evaluation of a pseudoceramide moisturizer in patients with mild-to-moderate atopic dermatitis. Dermatol Ther. 2014;4(1):83–92.

    Article  Google Scholar 

  30. Andrews S, Lee JW, Prausnitz M. Recovery of skin barrier after stratum corneum removal by microdermabrasion. AAPS PharmSciTech. 2011;12(4):1393–400.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Welss T, Basketter DA, Schröder KR. In vitro skin irritation: facts and future. State of the art review of mechanisms and models. Toxicol in Vitro. 2004;18(3):231–43.

    Article  CAS  PubMed  Google Scholar 

  32. Faller C, Bracher M, Dami N, Roguet R. Predictive ability of reconstructed human epidermis equivalents for the assessment of skin irritation of cosmetics☆☆This study is part of the European project SMT4-CT 97–2174: “Testing and improvement of reconstructed skin kits in order to elaborate European standards”. Toxicol in Vitro. 2002;16(5):557–72.

    Article  CAS  PubMed  Google Scholar 

  33. Schäfer-Korting M, Mahmoud A, Borgia SL, Brüggener B, Kleuser B, Schreiber S, et al. Reconstructed epidermis and full-thickness skin for absorption testing: influence of the vehicles used on steroid permeation. Altern Lab Anim. 2008;36(4):441–52.

    Article  PubMed  Google Scholar 

  34. Sekkat N, Kalia YN, Guy RH. Biophysical study of porcine ear skin in vitro and its comparison to human skin in vivo. J Pharm Sci. 2002;91(11):2376–81.

    Article  CAS  PubMed  Google Scholar 

  35. Barbero AM, Frasch HF. Pig and guinea pig skin as surrogates for human in vitro penetration studies: a quantitative review. Toxicol in Vitro. 2009;23(1):1–13.

    Article  CAS  PubMed  Google Scholar 

  36. Danso MO, Berkers T, Mieremet A, Hausil F, Bouwstra JA. An ex vivo human skin model for studying skin barrier repair. Exp Dermatol. 2015;24(1):48–54.

    Article  CAS  PubMed  Google Scholar 

  37. Abrams K, Harvell JD, Shriner D, Wertz P, Maibach H, Maibach HI, et al. Effect of organic solvents on in vitro human skin water barrier function. J Invest Dermatol. 1993;101(4):609–13.

    Article  CAS  PubMed  Google Scholar 

  38. Barba C, Alonso C, Martí M, Manich A, Coderch L. Skin barrier modification with organic solvents. Biochim Biophys Acta (BBA)- Biomembr. 2016;1858(8):1935–43.

    Article  CAS  Google Scholar 

  39. Wolf R, Parish LC. Effect of soaps and detergents on epidermal barrier function. Clin Dermatol. 2012;30(3):297–300.

    Article  PubMed  Google Scholar 

  40. Klang V, Schwarz JC, Lenobel B, Nadj M, Auböck J, Wolzt M, et al. In vitro vs. in vivo tape stripping: validation of the porcine ear model and penetration assessment of novel sucrose stearate emulsions. Eur J Pharm Biopharm. 2012;80(3):604–14.

    Article  CAS  PubMed  Google Scholar 

  41. Lademann J, Jacobi U, Surber C, Weigmann HJ, Fluhr JW. The tape stripping procedure – evaluation of some critical parameters. Eur J Pharm Biopharm. 2009;72(2):317–23.

    Article  CAS  PubMed  Google Scholar 

  42. Tsai JC, Sheu HM, Hung PL, Cheng CL. Effect of barrier disruption by acetone treatment on the permeability of compounds with various lipophilicities: implications for the permeability of compromised skin. J Pharm Sci. 2001;90(9):1242–54.

    Article  CAS  PubMed  Google Scholar 

  43. Löffler H, Dreher F, Maibach HI. Stratum corneum adhesive tape stripping: influence of anatomical site, application pressure, duration and removal. Br J Dermatol. 2004;151(4):746–52.

    Article  PubMed  Google Scholar 

  44. Rissmann R, Oudshoorn MHM, Hennink WE, Ponec M, Bouwstra JA. Skin barrier disruption by acetone: observations in a hairless mouse skin model. Arch Dermatol Res. 2009;301(8):609–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Fluhr JW, Feingold KR, Elias PM. Transepidermal water loss reflects permeability barrier status: validation in human and rodent in vivo and ex vivo models. Exp Dermatol. 2006;15(7):483–92.

    Article  PubMed  Google Scholar 

  46. Siewert M, Dressman J, Brown CK, Shah VP, Aiache J-M, Aoyagi N, et al. FIP/AAPS guidelines to dissolution/in vitro release testing of novel/special dosage forms. AAPS PharmSciTech. 2003;4(1):43–52.

    Article  CAS  PubMed Central  Google Scholar 

  47. Chilcott RP, Dalton CH, Emmanuel AJ, Allen CE, Bradley ST. Transepidermal water loss does not correlate with skin barrier function in vitro. J Invest Dermatol. 2002;118(5):871–5.

    Article  CAS  PubMed  Google Scholar 

  48. Levin J, Maibach H. The correlation between transepidermal water loss and percutaneous absorption: an overview. J Control Release. 2005;103(2):291–9.

    Article  CAS  PubMed  Google Scholar 

  49. Čuříková BA, Procházková K, Filková B, Diblíková P, Svoboda J, Kováčik A, et al. Simplified stratum corneum model membranes for studying the effects of permeation enhancers. Int J Pharm. 2017;534(1):287–96.

    Article  PubMed  Google Scholar 

  50. Kopecna M, Machacek M, Prchalova E, Stepanek P, Drasar P, Kotora M, et al. Dodecyl amino glucoside enhances transdermal and topical drug delivery via reversible interaction with skin barrier lipids. Pharm Res. 2017;34(3):640–53.

    Article  CAS  PubMed  Google Scholar 

  51. Lasch J, Weissig V, Brandl MJLapa. Preparation of liposomes. 2003;2:24-5.

  52. Sochorová M, Staňková K, Pullmannová P, Kováčik A, Zbytovská J, Vávrová K. Permeability barrier and microstructure of skin lipid membrane models of impaired glucosylceramide processing. Sci Rep. 2017;7(1).

  53. Gysler A, Kleuser B, Sippl W, Lange K, Korting HC, Höltje H-D, et al. Skin penetration and metabolism of topical glucocorticoids in reconstructed epidermis and in excised human skin. Pharm Res. 1999;16(9):1386–91.

    Article  CAS  PubMed  Google Scholar 

  54. Carrer V, Guzmán B, Martí M, Alonso C, Coderch L. Lanolin-based synthetic membranes as percutaneous absorption models for transdermal drug delivery. Pharmaceutics. 2018;10(3):73.

    Article  CAS  PubMed Central  Google Scholar 

  55. Kopečná M, Macháček M, Prchalová E, Štěpánek P, Drašar P, Kotora M, et al. Galactosyl pentadecene reversibly enhances transdermal and topical drug delivery. Pharm Res. 2017;34(10):2097–108.

    Article  PubMed  Google Scholar 

  56. Buraczewska I, Berne B, Lindberg M, Törmä H, Lodén MJBJoD. Changes in skin barrier function following long‐term treatment with moisturizers, a randomized controlled trial. 2007;156(3):492–8.

  57. Yang L, Mao-QlAng M, Taljebini M, Elias PM, Feingold KR. Topical stratum corneum lipids accelerate barrier repair after tape stripping, solvent treatment and some but not all types of detergent treatment. Br J Dermatol. 1995;133(5):679–85.

    Article  CAS  PubMed  Google Scholar 

  58. Visscher MO, Hoath SB, Conroy E, Wickett RR. Effect of semipermeable membranes on skin barrier repair following tape stripping. Arch Dermatol Res. 2001;293(10):491–9.

    Article  CAS  PubMed  Google Scholar 

  59. Hathout RM, Mansour S, Mortada ND, Geneidi AS, Guy RH. Uptake of microemulsion components into the stratum corneum and their molecular effects on skin barrier function. Mol Pharm. 2010;7(4):1266–73.

    Article  CAS  PubMed  Google Scholar 

  60. Yu G, Zhang G, Flach C, Mendelsohn R. Vibrational spectroscopy and microscopic imaging: novel approaches for comparing barrier physical properties in native and human skin equivalents. J Biomed Opt. 2012;18(6):061207.

    Article  Google Scholar 

  61. Clancy MJ, Corish J, Corrigan OI. A comparison of the effects of electrical current and penetration enhancers on the properties of human skin using spectroscopie (FTIR) and calorimetric (DSC) methods. Int J Pharm. 1994;105(1):47–56.

    Article  CAS  Google Scholar 

  62. Jacobi U, Weigmann HJ, Ulrich J, Sterry W, Lademann J. Estimation of the relative stratum corneum amount removed by tape stripping. Skin Res Technol. 2005;11(2):91–6.

    Article  CAS  PubMed  Google Scholar 

  63. Kalia YN, Alberti I, Sekkat N, Curdy C, Naik A, Guy RH. Normalization of stratum corneum barrier function and transepidermal water loss in vivo. Pharm Res. 2000;17(9):1148–50.

    Article  CAS  PubMed  Google Scholar 

  64. Gao Y, Wang X, Chen S, Li S, Liu X. Acute skin barrier disruption with repeated tape stripping: an in vivo model for damage skin barrier. Skin Res Technol. 2013;19(2):162–8.

    Article  PubMed  Google Scholar 

  65. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959;37(1):911–7.

    Article  CAS  PubMed  Google Scholar 

  66. Di Nardo A, Wertz P, Giannetti A, Seidenari S. Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. 1998.

  67. Mitragotri S. Modeling skin permeability to hydrophilic and hydrophobic solutes based on four permeation pathways. J Control Rel. 2003;86(1):69–92.

    Article  CAS  Google Scholar 

  68. Johnson ME, Berk DA, Blankschtein D, Golan DE, Jain RK, Langer RS. Lateral diffusion of small compounds in human stratum corneum and model lipid bilayer systems. Biophys J. 1996;71(5):2656–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Jacobi U, Taube H, Schäfer UF, Sterry W, Lademann J. Comparison of four different in vitro systems to study the reservoir capacity of the stratum corneum. J Control Release. 2005;103(1):61–71.

    Article  CAS  PubMed  Google Scholar 

  70. Rougier A, Rallis M, Krien P, Lotte C. In vivo percutaneous absorption: a key role for stratum corneum/vehicle partitioning. Arch Dermatol Res. 1990;282(8):498–505.

    Article  CAS  PubMed  Google Scholar 

  71. Fartasch M. Ultrastructure of the epidermal barrier after irritation. Microsc Res Tech. 1997;37(3):193–9.

    Article  CAS  PubMed  Google Scholar 

  72. Patil S, Singh P, Sarasour K, Maibach H. Quantification of sodium lauryl sulfate penetration into the skin and underlying tissues after topical application—pharmacological and toxicological implications. J Pharm Sci. 1995;84(10):1240–4.

    Article  CAS  PubMed  Google Scholar 

  73. di Nardo A, Sugino K, Wertz P, Ademola J, Maibach HI. Sodium lauryl sulfate (SLS) induced irritant contact dermatitis: a correlation study between ceramides and in vivo parameters of irritation. Contact Dermatitis. 1996;35(2):86–91.

    Article  PubMed  Google Scholar 

  74. Lévêque JL, de Rigal J, Saint-Léger D, Billy D. How does sodium lauryl sulfate alter the skin barrier function in man? A multiparametric approach. Skin Pharmacol Physiol. 1993;6(2):111–5.

    Article  Google Scholar 

  75. Froebe CL, Simion FA, Rhein LD, Cagan RH, Kligman A. Stratum corneum lipid removal by surfactants: relation to in vivo irritation. Dermatology. 1990;181(4):277–83.

    Article  CAS  Google Scholar 

  76. Čuříková-Kindlová BA, Diat O, Štěpánek F, Vávrová K, Zbytovská J. Probing the interactions among sphingosine and phytosphingosine ceramides with non- and alpha-hydroxylated acyl chains in skin lipid model membranes. Int J Pharm. 2019;563:384–94.

    Article  PubMed  Google Scholar 

  77. Lodén M, Bárány E. Skin-identical lipids versus petrolatum in the treatment of tape-stripped and detergent-perturbed human skin. Acta Derm-Venereol. 2000;80(6):412–5.

    Article  PubMed  Google Scholar 

  78. Hatziantoniou S, Rallis M, Demetzos C, Papaioannou GT. Pharmacological activity of natural lipids on a skin barrier disruption model. Pharmacol Res. 2000;42(1):55–9.

    Article  CAS  PubMed  Google Scholar 

  79. De Paepe K, Roseeuw D, Rogiers V. Repair of acetone- and sodium lauryl sulphate-damaged human skin barrier function using topically applied emulsions containing barrier lipids. J Eur Acad Dermatol Venereol. 2002;16(6):587–94.

    Article  PubMed  Google Scholar 

  80. Man M-Q, Feingold KR, Elias PM. Exogenous lipids influence permeability barrier recovery in acetone-treated murine skin. Arch Dermatol. 1993;129(6):728–38.

    Article  CAS  PubMed  Google Scholar 

  81. Verma DD, Verma S, Blume G, Fahr A. Particle size of liposomes influences dermal delivery of substances into skin. Int J Pharm. 2003;258(1):141–51.

    Article  CAS  PubMed  Google Scholar 

  82. de Pera M, Coderch L, Fonollosa J, de la Maza A, Parra JL. Effect of internal wool lipid liposomes on skin repair. Skin Pharmacol Physiol. 2000;13(3–4):188–95.

    Article  Google Scholar 

  83. Kucharekova M, Schalkwijk J, Van De Kerkhof PCM, Van De Valk PGM. Effect of a lipid-rich emollient containing ceramide 3 in experimentally induced skin barrier dysfunction. Contact Dermatitis. 2002;46(6):331–8.

    Article  CAS  PubMed  Google Scholar 

  84. Lynde CW, Andriessen A. A cohort study on a ceramide-containing cleanser and moisturizer used for atopic dermatitis. Cutis. 2014;93(4):207–13.

    PubMed  Google Scholar 

  85. Sahle FF, Gebre-Mariam T, Dobner B, Wohlrab J, Neubert RHH. Skin diseases associated with the depletion of stratum corneum lipids and stratum corneum lipid substitution therapy. Skin Pharmacol Physiol. 2015;28(1):42–55.

    Article  CAS  PubMed  Google Scholar 

  86. Zhang Q, Flach CR, Mendelsohn R, Mao G, Pappas A, Mack MC, et al. Topically applied ceramide accumulates in skin glyphs. Clin Cosmet Investig Dermatol. 2015;8:329–37.

    PubMed  PubMed Central  Google Scholar 

  87. Sjövall P, Skedung L, Gregoire S, Biganska O, Clément F, Luengo GS. Imaging the distribution of skin lipids and topically applied compounds in human skin using mass spectrometry. Sci Rep. 2018;8(1):16683.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Imokawa G, Akasaki S, Minematsu Y, Kawai M. Importance of intercellular lipids in water-retention properties of the stratum corneum: induction and recovery study of surfactant dry skin. Arch Dermatol Res. 1989;281(1):45–51.

    Article  CAS  PubMed  Google Scholar 

  89. Schoenwald RD, Stewart P. Effect of particle size on ophthalmic bioavailability of dexamethasone suspensions in rabbits. J Pharm Sci. 1980;69(4):391–4.

    Article  CAS  PubMed  Google Scholar 

  90. Lippacher A, Müller RH, Mäder K. Liquid and semisolid SLNTM dispersions for topical application: rheological characterization. Eur J Pharm Biopharm. 2004;58(3):561–7.

    Article  CAS  PubMed  Google Scholar 

  91. du Plessis J, Ramachandran C, Weiner N, Müller DG. The influence of particle size of liposomes on the deposition of drug into skin. Int J Pharm. 1994;103(3):277–82.

    Article  Google Scholar 

  92. Sakuyama S, Hirabayashi C, Hasegawa J-I, Yoshida S. Analysis of human face skin surface molecules in situ by Fourier-transform infrared spectroscopy. Skin Res Technol. 2010;16(2):151–60.

    Article  PubMed  Google Scholar 

  93. Brancaleon L, Bamberg MP, Sakamaki T, Kollias N. Attenuated total reflection–Fourier transform infrared spectroscopy as a possible method to investigate biophysical parameters of stratum corneum in vivo. J Invest Dermatol. 2001;116(3):380–6.

    Article  CAS  PubMed  Google Scholar 

  94. Boncheva M, Damien F, Normand V. Molecular organization of the lipid matrix in intact Stratum corneum using ATR-FTIR spectroscopy. Biochim Biophys Acta (BBA) - Biomembr. 2008;1778(5):1344–55.

    Article  CAS  Google Scholar 

  95. Bernard G, Auger M, Soucy J, Pouliot R. Physical characterization of the stratum corneum of an in vitro psoriatic skin model by ATR-FTIR and Raman spectroscopies. Biochim Biophys Acta (BBA) - Gen Subj. 2007;1770(9):1317–23.

    Article  CAS  Google Scholar 

  96. He W, Guo X, Xiao L, Feng M. Study on the mechanisms of chitosan and its derivatives used as transdermal penetration enhancers. Int J Pharm. 2009;382(1):234–43.

    Article  CAS  PubMed  Google Scholar 

  97. Schwarz JC, Klang V, Hoppel M, Mahrhauser D, Valenta C. Natural microemulsions: formulation design and skin interaction. Eur J Pharm Biopharm. 2012;81(3):557–62.

    Article  CAS  PubMed  Google Scholar 

  98. Pilgram GSK, Vissers DCJ, van der Meulen H, Koerten HK, Pavel S, Lavrijsen SPM, et al. Aberrant lipid organization in stratum corneum of patients with atopic dermatitis and lamellar ichthyosis. J Invest Dermatol. 2001;117(3):710–7.

    Article  CAS  PubMed  Google Scholar 

  99. Gorcea M, Hadgraft J, Moore DJ, Lane ME. In vivo barrier challenge and initial recovery in human facial skin. Skin Res Technol. 2013;19(1):e375–82.

    Article  PubMed  Google Scholar 

  100. Ramsing DW, Agner T. Effect of glove occlusion on human skin (II). Contact Dermatitis. 1996;34(4):258–62.

    Article  CAS  PubMed  Google Scholar 

  101. Zhai H, Maibach HI. Occlusion vs. skin barrier function. Skin Res Technol. 2002;8(1):1–6.

    Article  PubMed  Google Scholar 

  102. Iikura H, Uchida K, Ogawa-Fuse C, Bito K, Naitou S, Hosokawa M, et al. Effects of temperature and humidity on the skin permeation of hydrophilic and hydrophobic drugs. AAPS PharmSciTech. 2019;20(7):264.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was financially supported by the Czech Science Foundation (GACR19-09600S). Evonik is gratefully acknowledged for donating ceramides. We would like to thank Radek Stibor for providing the porcine skin.

Funding

This study was financially supported by the Czech Science Foundation (project GACR19-09600S).

Author information

Authors and Affiliations

  1. Faculty of Chemical Technology, Department of Organic Technology, University of Chemistry and Technology Prague, Technická 5, 166 28, Prague, Czech Republic

    Barbora Amélie Čuříková-Kindlová, Aneta Vovesná & Jarmila Zbytovská

  2. Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic

    Anna Nováčková

Authors
  1. Barbora Amélie Čuříková-Kindlová
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aneta Vovesná
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anna Nováčková
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jarmila Zbytovská
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

BAC-K performed the permeation and FTIR experiments, analyzed the data, and wrote the manuscript. AV prepared the samples, performed the permeation experiments, and reviewed the manuscript. AN performed the DSC measurements, evaluated the data, and reviewed the manuscript. JZ conceived the project, designed the experiments, analyzed the data, and wrote the manuscript. The authors have read the manuscript and approved its submission.

Corresponding author

Correspondence to Jarmila Zbytovská.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 183 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Čuříková-Kindlová, B.A., Vovesná, A., Nováčková, A. et al. In Vitro Modeling of Skin Barrier Disruption and its Recovery by Ceramide-Based Formulations. AAPS PharmSciTech 23, 21 (2022). https://doi.org/10.1208/s12249-021-02154-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-021-02154-z

KEY WORDS

Search

Navigation