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In Vivo Imaging of ZnO Nanoparticles from Sunscreen on Human Skin with a Mobile Multiphoton Tomograph

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Abstract

Reports on the toxicity of inorganic nanoparticles used in sunscreen, in particular of zinc oxide and titanium dioxide, have raised concerns about a possible particle penetration through the skin barrier. We used two-photon imaging to visualize the distribution of zinc-oxide nanoparticles after topical application of a commercially available sunscreen on human skin in vivo and to investigate a possible penetration of nanoparticles beyond the stratum corneum. Two-photon imaging is in particular suitable for these investigations since the excitation and the nonlinear signal light from zinc-oxide nanoparticles as well as the endogenous skin autofluorescence are all spectrally well-separated which allows a clear identification of the signal origin by detection in two-spectral channels. Furthermore, microscopic modifications in the cutaneous structure like skin wrinkles which exhibit different thicknesses of the dermal layers and at the same time are regions where nanoparticle accumulation can be specifically investigated. The results indicate no penetration of nanoparticle through the barrier of the stratum corneum of healthy skin even in microscopic wrinkles.

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References

  1. Sheehan, J. M., Potten, C. S., Young, A. R. (1998). Tanning in human skin types II and III offers modest photoprotection against erythema. Photochemistry and Photobiology, 68(4), 588–592.

    Article  Google Scholar 

  2. de Winter, S., Vink, A. A., Roza, L., Pavel, S. (2001). Solar-simulated skin adaptation and its effect on subsequent UV-induced epidermal DNA damage. The Journal of Investigative Dermatology, 117(3), 678–682. doi:10.1046/j.0022-202x.2001.01478.x.

    Article  Google Scholar 

  3. Pathak, M. A. (1982). Sunscreens: topical and systemic approaches for protection of human skin against harmful effects of solar radiation. Journal of the American Academy of Dermatology, 7(3), 285–312.

    Article  Google Scholar 

  4. Young, A. R., Sheehan, J. M., Chadwick, C. A., Potten, C. S. (2000). Protection by ultraviolet A and B sunscreens against in situ dipyrimidine photolesions in human epidermis is comparable to protection against sunburn. The Journal of Investigative Dermatology, 115(1), 37–41. doi:10.1046/j.1523-1747.2000.00012.x.

    Article  Google Scholar 

  5. Sambandan, D. R., & Ratner, D. (2011). Sunscreens: an overview and update. Journal of the American Academy of Dermatology, 64(4), 748–758. doi:10.1016/j.jaad.2010.01.005.

    Article  Google Scholar 

  6. Burnett, M. E., & Wang, S. Q. (2011). Current sunscreen controversies: a critical review. Photodermatology Photoimmunology, 27(2), 58–67.

    Article  Google Scholar 

  7. Smijs, T. G., & Pavel, S. (2011). Titanium dioxide and zinc oxide nanoparticles in sunscreens: focus on their safety and effectiveness. Nanotechnology, Science and Applications, 4, 95–112.

    Article  Google Scholar 

  8. Serpone, N., Dondi, D., Albini, A. (2007). Inorganic and organic UV filters: their role and efficacy in sunscreens and suncare product. Inorganica Chimica Acta, 360(3), 794–802.

    Article  Google Scholar 

  9. Nohynek, G. J., & Dufour, E. K. (2012). Nano-sized cosmetic formulations or solid nanoparticles in sunscreens: a risk to human health? Archives of Toxicology, 86(7), 1063–1075. doi:10.1007/s00204-012-0831-5.

    Article  Google Scholar 

  10. Baroli, B. (2010). Penetration of nanoparticles and nanomaterials in the skin: fiction or reality? Journal of Pharmaceutical Sciences, 99(1), 21–50. doi:10.1002/jps.21817.

    Article  Google Scholar 

  11. Sharma, V., Shukla, R. K., Saxena, N., Parmar, D., Das, M., Dhawan, A. (2009). DNA damaging potential of zinc oxide nanoparticles in human epidermal cells. Toxicology Letters, 185(3), 211–218. doi:10.1016/j.toxlet.2009.01.008.

    Article  Google Scholar 

  12. Newman, M. D., Stotland, M., Ellis, J. I. (2009). The safety of nanosized particles in titanium dioxide- and zinc oxide-based sunscreens. Journal of the American Academy of Dermatology, 61(4), 685–692. doi:10.1016/j.jaad.2009.02.051.

    Article  Google Scholar 

  13. Detoni, C. B., Coradini, K., Back, P., Oliveira, C. M., Andrade, D. F., Beck, R. C. R., et al. (2014). Penetration, photo-reactivity and photoprotective properties of nanosized ZnO. Photochemical & Photobiological Sciences, 13(9), 1253–1260. doi:10.1039/C3PP50373A.

    Article  Google Scholar 

  14. Gamer, A. O., Leibold, E., van Ravenzwaay, B. (2006). The in vitro absorption of microfine zinc oxide and titanium dioxide through porcine skin. Toxicology In vitro: An International Journal Published in Association with BIBRA, 20(3), 301–307. doi:10.1016/j.tiv.2005.08.008.

    Article  Google Scholar 

  15. Schulz, J., Hohenberg, H., Pflucker, F., Gartner, E., Will, T., Pfeiffer, S., et al. (2002). Distribution of sunscreens on skin. Advanced Drug Delivery Reviews, 54, S157–S163. doi:10.1016/S0169-409x(02)00120-5.

    Article  Google Scholar 

  16. Cross, S. E., Innes, B., Roberts, M. S., Tsuzuki, T., Robertson, T. A., McCormick, P. (2007). Human skin penetration of sunscreen nanoparticles: in-vitro assessment of a novel micronized zinc oxide formulation. Skin Pharmacology Physiology, 20(3), 148–154. doi:10.1159/000098701.

    Article  Google Scholar 

  17. Monteiro-Riviere, N. A., Wiench, K., Landsiedel, R., Schulte, S., Inman, A. O., Riviere, J. E. (2011). Safety evaluation of sunscreen formulations containing titanium dioxide and zinc oxide nanoparticles in UVB sunburned skin: an in vitro and in vivo study. Toxicological Sciences, 123(1), 264–280.

    Article  Google Scholar 

  18. Leite-Silva, V. R., Le Lamer, M., Sanchez, W. Y., Liu, D. C., Sanchez, W. H., Morrow, I., et al. (2013). The effect of formulation on the penetration of coated and uncoated zinc oxide nanoparticles into the viable epidermis of human skin in vivo. European Journal of Pharmaceutics and Biopharmaceutics, 84(2), 297–308.

    Article  Google Scholar 

  19. Zvyagin, A. V., Zhao, X., Gierden, A., Sanchez, W., Ross, J. A., Roberts, M. S. (2008). Imaging of zinc oxide nanoparticle penetration in human skin in vitro and in vivo. Journal of Biomedical Optics, 13(6), 064031.

    Article  Google Scholar 

  20. Darvin, M. E., König, K., Kellner-Hoefer, M., Breunig, H. G., Werncke, W., Meinke, M. C., et al. (2012). Safety assessment by multiphoton fluorescence/second harmonic generation/hyper-Rayleigh scattering tomography of ZnO nanoparticles used in cosmetic products. Skin Pharmacology Physiology, 25(4), 219–226.

    Article  Google Scholar 

  21. Labouta, H. I., & Schneider, M. (2013). Interaction of inorganic nanoparticles with the skin barrier: current status and critical review. Nanomedicine-Nanotechnology, 9(1), 39–54. doi:10.1016/j.nano.2012.04.004.

    Article  Google Scholar 

  22. Detoni, C. B., Coradini, K., Back, P., Oliveira, C. M., Andrade, D. F., Beck, R. C., et al. (2014). Penetration, photo-reactivity and photoprotective properties of nanosized ZnO. Photochemical and Photobiological Sciences: Official Journal of the European Photochemistry Association and the European Society for Photobiology. doi:10.1039/c3pp50373a.

    Google Scholar 

  23. Gulson, B., McCall, M., Korsch, M., Gomez, L., Casey, P., Oytam, Y., et al. (2010). Small amounts of zinc from zinc oxide particles in sunscreens applied outdoors are absorbed through human skin. Toxicological Sciences, 118(1), 140–149. doi:10.1093/toxsci/kfq243.

    Article  Google Scholar 

  24. Wu, J. H., Liu, W., Xue, C. B., Zhou, S. C., Lan, F. L., Bi, L., et al. (2009). Toxicity and penetration of TiO2 nanoparticles in hairless mice and porcine skin after subchronic dermal exposure. Toxicology Letters, 191(1), 1–8. doi:10.1016/j.toxlet.2009.05.020.

    Article  Google Scholar 

  25. Baroli, B., Ennas, M. G., Loffredo, F., Isola, M., Pinna, R., Lopez-Quintela, M. A. (2007). Penetration of metallic nanoparticles in human full-thickness skin. Journal of Investigative Dermatology, 127(7), 1701–1712. doi:10.1038/sj.jid.5700733.

    Google Scholar 

  26. Filipe, P., Silva, J. N., Silva, R., de Castro, J. L. C., Gomes, M. M., Alves, L. C., et al. (2009). Stratum corneum is an effective barrier to TiO2 and ZnO nanoparticle percutaneous absorption. Skin Pharmacology Physiology, 22(5), 266–275. doi:10.1159/000235554.

    Article  Google Scholar 

  27. König, K., Raphael, A. P., Lin, L., Grice, J. E., Soyer, H. P., Breunig, H. G., et al. (2011). Applications of multiphoton tomographs and femtosecond laser nanoprocessing microscopes in drug delivery research. Advanced Drug Delivery Reviews, 63(4–5), 388–404. doi:10.1016/j.addr.2011.03.002.

    Article  Google Scholar 

  28. Breunig, H. G., Studier, H., König, K. (2010). Multiphoton excitation characteristics of cellular fluorophores of human skin in vivo. Optics Express, 18(8), 7857–7871.

    Article  Google Scholar 

  29. Masters, B. R., So, P. T., Gratton, E. (1997). Multiphoton excitation fluorescence microscopy and spectroscopy of in vivo human skin. Biophysical Journal, 72(6), 2405–2412. doi:10.1016/S0006-3495(97)78886-6.

    Article  Google Scholar 

  30. Kachynski, A. V., Kuzmin, A. N., Nyk, M., Roy, I., Prasad, P. N. (2008). Zinc oxide nanocrystals for nonresonant nonlinear optical microscopy in biology and medicine. Journal of Physical Chemistry C, 112(29), 10721–10724. doi:10.1021/Jp801684j.

    Article  Google Scholar 

  31. Zipfel, W. R., Williams, R. M., Christie, R., Nikitin, A. Y., Hyman, B. T., Webb, W. W. (2003). Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. PNAS, 100(12), 7075–7080. doi:10.1073/pnas.0832308100.

    Article  Google Scholar 

  32. Laiho, L. H., Pelet, S., Hancewicz, T. M., Kaplan, P. D., So, P. T. C. (2005). Two-photon 3-D mapping of ex vivo human skin endogenous fluorescence species based on fluorescence emission spectra. Journal of Biomedical Optics, 10(2).

  33. Weinigel, M., Breunig, H. G., Kellner-Hofer, M., Buckle, R., Darvin, M. E., Klemp, M., et al. (2014). In vivo histology: optical biopsies with chemical contrast using clinical multiphoton/coherent anti-Stokes Raman scattering tomography. Laser Physical Letters, 11(5).

  34. Breunig HG., König K. (2011). Spectral characteristics of two-photon autofluorescence and second harmonic generation from human skin in vivo. Proc of SPIE 7883:788311-788311-788319.

  35. Song, Z., Kelf, T. A., Sanchez, W. H., Roberts, M. S., Ricka, J., Frenz, M., et al. (2011). Characterization of optical properties of ZnO nanoparticles for quantitative imaging of transdermal transport. Biomedicine Optic Express, 2(12), 3321–3333.

    Article  Google Scholar 

  36. Lewicka, Z. A., Yu, W. W., Oliva, B. L., Contreras, E. Q., Colvin, V. L. (2013). Photochemical behavior of nanoscale TiO2 and ZnO sunscreen ingredients. Journal Photochemistry Photobiology A, 263, 24–33. doi:10.1016/j.jphotochem.2013.04.019.

    Article  Google Scholar 

  37. Contet-Audonneau, J. L., Jeanmarie, C., Pauly, G. (1999). A histological study of human wrinkle structures: comparison between sun-exposed areas of the face, with or without wrinkles, and sun-protected areas. British Journal Dermatology, 140(6), 1038–1047.

    Article  Google Scholar 

  38. Lin, L. L., Grice, J. E., Butler, M. K., Zvyagin, A. V., Becker, W., Robertson, T. A., et al. (2011). Time-correlated single photon counting for simultaneous monitoring of zinc oxide nanoparticles and NAD(P)H in intact and barrier-disrupted volunteer skin. Pharmacy Res-Dordr, 28(11), 2920–2930. doi:10.1007/s11095-011-0515-5.

    Article  Google Scholar 

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Breunig, H.G., Weinigel, M. & König, K. In Vivo Imaging of ZnO Nanoparticles from Sunscreen on Human Skin with a Mobile Multiphoton Tomograph. BioNanoSci. 5, 42–47 (2015). https://doi.org/10.1007/s12668-014-0155-4

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  • DOI: https://doi.org/10.1007/s12668-014-0155-4

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