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Stabilization of Lipid Lamellar Bilayer Structure of Stratum Corneum Modulated by Poly (2-methacryloyloxyethyl phosphorylcholine) in Relation to Skin Hydration and Skin Protection



One crucial factor in skin tissue engineering is to understand the hydration and barrier property of skin. We investigated the skin hydration and stabilization strategy of inter-lamellar structure of stratum corneum (SC) using poly (2-methacryloyloxyethyl phosphorylcholine) (PMPC).


The unique hydration and stabilization potency of PMPC on the barrier function of the SC examined using freshly excised hairless mouse skin as a model membrane and the relationship between the stabilization of the lipid lamellar bilayer (LLB) and its enhanced water holding capacity was established.


Differential scanning calorimeter based on the phase-transition temperature of lipid domain of SC demonstrated that PMPC stabilized the LLB. The ratio of the heat of lipid phase transition (△H) of SC exposed to water and PMPC for 24 h was 1.51. X-ray crystallography showed the presence of well- organized lipids in intercellular membranes exhibiting short and long periodicity of lamellar phases. The peak at 4.4 nm attributed to the long periodicity phase (LPP) was missing in water-treated SC, where, the presence of 4.2- 4.4 nm peak in PMPC treated SC indicated that PMPC stabilized LPP. Transmission electron microscopy study demonstrated that the LLB structure became more rigid and orderly in PMPC treated SC.


The unique ion paired structure of PMPC enhances the barrier function of the SC by stabilizing LLB structure and hydration by inducing weakly bound water. The unique hydration state and stabilization effect from extended water exposure could provide a valuable information to prepare reliable artificial skin matrix and skin tissue.

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  1. 1.

    Gay CL, Guy RH, Golden GM, Mak VH, Francoeur M. Characterization of low temperature (i.e. <65) lipid transitions in human stratum corneum. J Invest Dermatol. 1994;103:233–9.

    CAS  Article  Google Scholar 

  2. 2.

    Rawlings AV, Harding CR. Moisturization and skin barrier function. Dermatol Ther. 2014;17:43–8.

    Article  Google Scholar 

  3. 3.

    Mak VHW, Potts RO, Guy RH. Does hydration affect intercellular lipid organization in the stratum corneum? Pharm Res. 1991;8:1064–5.

    CAS  Article  Google Scholar 

  4. 4.

    Lee AR, Moon HK. Gravimetric analysis and differential scanning calorimetric studies on glycerin-induced skin hydration. Arch Pharm Res. 2007;30:1489–95.

    CAS  Article  Google Scholar 

  5. 5.

    Inoue T, Tsujii K, Okamoto K, Toda K. Differential scanning calorimetric studies on the melting behavior of water in stratum corneum. J Invest Dermatol. 1986;86:689–93.

    CAS  Article  Google Scholar 

  6. 6.

    Liron ZR, Wright RL, McDougal JN. Water diffusivity in porcine stratum corneum measured by a thermal gravimetric analysis technique. J Pharm Sci. 1994;83:457–62.

    CAS  Article  Google Scholar 

  7. 7.

    Ishihara K, Mu M, Konno T. Water-soluble and amphiphilic phospholipid copolymers having 2-methacryloyloxyethyl phosphorylcholine units for the solubilization of bioactive compounds. J Biomater Sci Polymer Ed. 2018;29:844–62.

    CAS  Article  Google Scholar 

  8. 8.

    Liron ZR, Clewell HJ, McDougal JN. Kinetics of water vapor sorption in porcine stratum corneum. J Pharm Sci. 1994;83:692–8.

    CAS  Article  Google Scholar 

  9. 9.

    Ishihara K, Nomura H, Mihara T, Kurita K, Iwasaki Y, Nakabayashi N. Why do phospholipid polymers reduce protein adsorption? J Biomed Mater Res. 1998;39:323–30.

    CAS  Article  Google Scholar 

  10. 10.

    Chit L, Bastien P, Biatry B, Simonnet JT, Potter A, Minondo AM, et al. In vitro and in vivo confocal Raman Study of human skin hydration: assessment of a new moisturizing agent pMPC. Biopolymers. 2007;85:359–69.

    Article  Google Scholar 

  11. 11.

    Kanekura T, Nagata Y, Miyoshi H, Ishihara K, Nakabayashi N, Kanzaki T. Beneficial effects of synthetic phospholipid polymer, poly (2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) on stratum corneum function. Clin Exp Dermatol. 2002;27:230–4.

    CAS  Article  Google Scholar 

  12. 12.

    Warner RR, Boissy YL, Lilly NA, Spears MJ, McKillop K, Marshall JL, et al. Water disrupts stratum corneum lipid lamellae: damage is similar to surfactants. J Invest Dermatol. 1999;13:960–6.

    Google Scholar 

  13. 13.

    Lee AR. Phospholipid polymer, 2-methacryloyloxyethyl phosphorylcholine and its skin barrier function. Arch Pharm Res. 2004;27:1177–82.

    CAS  Article  Google Scholar 

  14. 14.

    Hasegawa T, Kim S, Tsuchida M, Issiki Y, Kondo S, Sugibayashi K. Decrease in skin permeation and antibacterial effect of parabens by a polymeric additive, poly (2-methacryloylloxyethyl phosphorylcholie-co-butylmetacrylate. Chem Pharm Bull (Tokyo). 2005;53:271–6.

    CAS  Article  Google Scholar 

  15. 15.

    Summers RS, Summers B, Chandar P, Feinberg C. The effect of lipids, with and without humectant on skin xerosis. J Soc Cosmet Chem. 1996;47:27–39.

    CAS  Google Scholar 

  16. 16.

    Tanaka M, Okada M, Zhen YX, Inamura N, Kitano T, Shirai S, et al. Decrease hydration state of the stratum corneum and reduced amino acid content of the skin surface in patients with seasonal allergic rhinitis. Br J Dermatol. 1998;319:618–21.

    Article  Google Scholar 

  17. 17.

    Golden GM, Meckie JE, Potts RO. Role of stratum corneum lipid fluidity in transdermal drug flux. J Pharm Sci. 1987;76:25–8.

    CAS  Article  Google Scholar 

  18. 18.

    Liron ZR, Wright RL, McDougal JN. Water diffusivity by a thermal gravimetric analysis technique. J Pharm Sci. 1994;83:457–62.

    CAS  Article  Google Scholar 

  19. 19.

    Ohta N, Ban S, Tanaka H, Nakata S, Hatta I. Swelling of intercellular lipis lamellar structure with short repeat distance in hairless mouse stratum corneum as studied by x-ray diffraction. Chem Phys Lipids. 2003;123:1–8.

    CAS  Article  Google Scholar 

  20. 20.

    Bouwstra JA, Gooris GS, Bras W, Downing DT. Lipid organization in pig startum corneum. J Lipid Res. 1995;36:685–95.

    CAS  Article  Google Scholar 

  21. 21.

    Groen D, Gooris GS, Bouwstra JA. New Insights into the stratum corneum lipid organization by x-ray diffraction analysis. Biophysical J. 2009;97:2242–9.

    CAS  Article  Google Scholar 

  22. 22.

    Bouwstra JA, Gooris GS, Cheng K, Weerheim A, Bras W, Ponec M. Phase behavior of isolated skin lipids. J Lipid Res. 1998;37:999–1011.

    Article  Google Scholar 

  23. 23.

    Bouwstra JA, Gooris GS, Dubbelaar FE, Ponec M. Cholesterol sulfate and calcium affect stratum corneum lipid organization overa wide temperature range. J Lipid Res. 1999;40:2303–12.

    CAS  Article  Google Scholar 

  24. 24.

    Schreiner V, Gooris GS, Pfeiffer S, Lanzendörfer G, Wenck H, Diembeck W, et al. Barrier characteristics of different human skin types investigated with x-ray diffraction, lipid analysis, and electron microscopy imaging. J Invest Dermatol. 2000;114:654–60.

    CAS  Article  Google Scholar 

  25. 25.

    Ishihara K. Blood-compatible surfaces with phosphorylcholine-based polymers for cardiovascular medical devices. Langmuir. 2019;35:1778–87.

    CAS  Article  Google Scholar 

  26. 26.

    Ishihara K, Mu M, Konno T, Inoue Y, Fukazawa K. The unique hydration state of poly (2-methacryloyloxyethyl phosphorylcholine). J Biomater Sci Polymer Ed. 2017;28:884–99.

    CAS  Article  Google Scholar 

  27. 27.

    Shaku M, Kuroda H, Oba A, Okura S, Ishihara K, Nakabayashi N. Bifunctional Phospholipid polymer designed from dermatological points to enhance stratum corneum functions. In: Proceedings of Sixth World Biomaterials Congress, May 15-20. Transactions, Vol. 1, Hawaii; 2000. p.60.

  28. 28.

    Zhang Y, Kanetaka H, Sano Y, Kano M, Kudo TA, Shomozu Y. MPC polymer regulates fibrous formation by modulating cell adhesion to the biomaterial surface. Dent Mater J. 2010;29:518–28.

    Article  Google Scholar 

  29. 29.

    Blank IH, Moloney J, Emslie A, Simon I, Apt C. The diffusion of water across the stratum corneum as a function of its water content. J Invest Dermatol. 1984;82:188–94.

    CAS  Article  Google Scholar 

  30. 30.

    Lee AR. Microneedle-mediated delivery of cosmeceutically relevant nucleoside and peptides in human skin: challenges and strategies for dermal delivery. J Pharm Investig. 2019;49:587–601.

    CAS  Article  Google Scholar 

  31. 31.

    Schumitt T, Neubert RHH. State of the art in stratum corneum research: the biophysical properties of ceramides. Chem Phys Lipids. 2018;216:91–103.

    Article  Google Scholar 

  32. 32.

    Simard M, Julien P, Fradette J, Pouliot R. Modulation of the lipid profile of reconstructed skin substitutes after essential fatty acid supplementation affects testosterone permeability. Cells. 2019;8:1142–57.

    CAS  Article  Google Scholar 

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This work was supported in part by the Duksung Women’s University Research Grants 2020.

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Correspondence to Ae-Ri Cho Lee.

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The animal experiments were performed under animal protocol number (no. 2020-012-007) approved by the Duksung Women’s University Institutional Animal Care and Use Committee (IACUC).

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Cho Lee, AR., Moon, H. & Ishihara, K. Stabilization of Lipid Lamellar Bilayer Structure of Stratum Corneum Modulated by Poly (2-methacryloyloxyethyl phosphorylcholine) in Relation to Skin Hydration and Skin Protection. Tissue Eng Regen Med (2021).

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  • MPC
  • Phospholipid polymer
  • Skin hydration
  • Skin protection
  • Stratum corneum
  • Lipid lamellar bilayer