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A quantitative study of nanoparticle skin penetration with interactive segmentation

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Abstract

In the last decade, the application of nanotechnology techniques has expanded within diverse areas such as pharmacology, medicine, and optical science. Despite such wide-ranging possibilities for implementation into practice, the mechanisms behind nanoparticle skin absorption remain unknown. Moreover, the main mode of investigation has been qualitative analysis. Using interactive segmentation, this study suggests a method of objectively and quantitatively analyzing the mechanisms underlying the skin absorption of nanoparticles. Silica nanoparticles (SNPs) were assessed using transmission electron microscopy and applied to the human skin equivalent model. Captured fluorescence images of this model were used to evaluate degrees of skin penetration. These images underwent interactive segmentation and image processing in addition to statistical quantitative analyses of calculated image parameters including the mean, integrated density, skewness, kurtosis, and area fraction. In images from both groups, the distribution area and intensity of fluorescent silica gradually increased in proportion to time. Since statistical significance was achieved after 2 days in the negative charge group and after 4 days in the positive charge group, there is a periodic difference. Furthermore, the quantity of silica per unit area showed a dramatic change after 6 days in the negative charge group. Although this quantitative result is identical to results obtained by qualitative assessment, it is meaningful in that it was proven by statistical analysis with quantitation by using image processing. The present study suggests that the surface charge of SNPs could play an important role in the percutaneous absorption of NPs. These findings can help achieve a better understanding of the percutaneous transport of NPs. In addition, these results provide important guidance for the design of NPs for biomedical applications.

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References

  1. Anand N, Kumar D, Srinivasan R, Singh M (2003) Laser reflectance imaging of human forearms and their tissue-equivalent phantoms. Med Biol Eng Comput 41:28–32

    Article  CAS  PubMed  Google Scholar 

  2. Anoraganingrum D (1999) Cell segmentation with median filter and mathematical morphology operation. In: Proceedings of international conference on image analysis and processing, IEEE, pp 1043–1046

  3. Baba N, Ichise N, Tanaka T (1996) Image area extraction of biological objects from a thin section image by statistical texture analysis. J Electron Microsc 45:298–306

    Article  CAS  Google Scholar 

  4. Damour O, Augustin C, Black A (1998) Applications of reconstructed skin models in pharmaco-toxicological trials. Med Biol Eng Comput 36:825–832

    Article  CAS  PubMed  Google Scholar 

  5. Filon FL, Mauro M, Adami G, Bovenzi M, Crosera M (2015) Nanoparticles skin absorption: new aspects for a safety profile evaluation. Regul Toxicol Pharmacol 72:310–322

    Article  Google Scholar 

  6. Gabbanini S, Lucchi E, Carli M, Berlini E, Minghetti A, Valgimigli L (2009) In vitro evaluation of the permeation through reconstructed human epidermis of essentials oils from cosmetic formulations. J Pharm Biomed Anal 50:370–376

    Article  CAS  PubMed  Google Scholar 

  7. Goffredo M, Schmid M, Conforto S, Amorosi B, D’Alessio T, Palma C (2012) Quantitative color analysis for capillaroscopy image segmentation. Med Biol Eng Comput 50:567–574

    Article  PubMed  Google Scholar 

  8. Heinone T, Dastidar P, Kauppinen P, Malmivuo J, Eskola H (1998) Semi-automatic tool for segmentation and volumetric analysis of medical images. Med Biol Eng Comput 36:291–296

    Article  Google Scholar 

  9. Hemachander S, Verma A, Arora S, Panigrahi PK (2007) Locally adaptive block thresholding method with continuity constraint. Pattern Recogn Lett 28:119–124

    Article  Google Scholar 

  10. Jeong SH, Kim JH, Yi SM, Lee JP, Kim JH, Sohn KH, Park KL, Kim M-K, Son SW (2010) Assessment of penetration of quantum dots through in vitro and in vivo human skin using the human skin equivalent model and the tape stripping method. Biochem Biophys Res Commun 394:612–615

    Article  CAS  PubMed  Google Scholar 

  11. Kang C-C, Wang W-J (2007) A novel edge detection method based on the maximizing objective function. Pattern Recogn 40:609–618

    Article  Google Scholar 

  12. Kim B, Han G, Toley BJ, C-k Kim, Rotello VM, Forbes NS (2010) Tuning payload delivery in tumour cylindroids using gold nanoparticles. Nat Nanotechnol 5:465–472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kirjavainen M, Urtti A, Jääskeläinen I, Marjukka Suhonen T, Paronen P, Valjakka-Koskela R, Kiesvaara J, Mönkkönen J (1996) Interaction of liposomes with human skin in vitro–the influence of lipid composition and structure. Biochim Biophys Acta 1304:179–189

    Article  CAS  PubMed  Google Scholar 

  14. Lademann J, Richter H, Meinke MC, Lange-Asschenfeldt B, Antoniou C, Mak WC, Renneberg R, Sterry W, Patzelt A (2013) Drug delivery with topically applied nanoparticles: science fiction or reality. Skin Pharmacol Physiol 26:227–233

    Article  CAS  PubMed  Google Scholar 

  15. Lee O, Jeong SH, Shin WU, Lee G, Oh C, Son SW (2013) Influence of surface charge of gold nanorods on skin penetration. Skin Res Technol 19:e390–e396

    Article  PubMed  Google Scholar 

  16. Lezoray O, Cardot H (2002) Bayesian marker extraction for color watershed in segmenting microscopic images. In: Proceedings of 16th international conference on pattern recognition, IEEE, pp 739–742

  17. Llandro J, Palfreyman J, Ionescu A, Barnes C (2010) Magnetic biosensor technologies for medical applications: a review. Med Biol Eng Comput 48:977–998

    Article  CAS  PubMed  Google Scholar 

  18. Loizou CP (2014) A review of ultrasound common carotid artery image and video segmentation techniques. Med Biol Eng Comput 52:1073–1093

    Article  PubMed  Google Scholar 

  19. McInerney T, Terzopoulos D (2000) T-snakes: topology adaptive snakes. Med Image Anal 4:73–91

    Article  CAS  PubMed  Google Scholar 

  20. Mortensen LJ, Oberdörster G, Pentland AP, DeLouise LA (2008) In vivo skin penetration of quantum dot nanoparticles in the murine model: the effect of UVR. Nano Lett 8:2779–2787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Muerle JL, Allen DC (1968) Experimental evaluation of techniques for automatic segmentation of objects in a complex scene. Pict Pattern Recognit 3–13

  22. Nakazawa K, Kalassy M, Sahuc F, Collombel C, Damour O (1998) Pigmented human skin equivalent—as a model of the mechanisms of control of cell–cell and cell–matrix interactions. Med Biol Eng Comput 36:813–820

    Article  CAS  PubMed  Google Scholar 

  23. Osher S, Sethian JA (1988) Fronts propagating with curvature-dependent speed: algorithms based on Hamilton–Jacobi formulations. J Comput Phys 79:12–49

    Article  Google Scholar 

  24. Pelley JL, Daar AS, Saner MA (2009) State of academic knowledge on toxicity and biological fate of quantum dots. Toxicol Sci 112:276–296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Roguet R (1999) Use of skin cell cultures for in vitro assessment of corrosion and cutaneous irritancy. Cell Biol Toxicol 15:63–75

    Article  CAS  PubMed  Google Scholar 

  26. Ryman-Rasmussen JP, Riviere JE, Monteiro-Riviere NA (2006) Penetration of intact skin by quantum dots with diverse physicochemical properties. Toxicol Sci 91:159–165

    Article  CAS  PubMed  Google Scholar 

  27. Schneider M, Stracke F, Hansen S, Schaefer UF (2009) Nanoparticles and their interactions with the dermal barrier. Dermatoendocrinol 1:197–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sethian JA (2003) Level set methods and fast marching methods. J Comput Inf Technol 11:1–2

    Article  Google Scholar 

  29. Sinico C, Manconi M, Peppi M, Lai F, Valenti D, Fadda AM (2005) Liposomes as carriers for dermal delivery of tretinoin: in vitro evaluation of drug permeation and vesicle–skin interaction. J Controlled Release 103:123–136

    Article  CAS  Google Scholar 

  30. Su D, Ma R, Zhu L (2011) Numerical study of nanofluid infusion in deformable tissues for hyperthermia cancer treatments. Med Biol Eng Comput 49:1233–1240

    Article  PubMed  Google Scholar 

  31. Tian H, Srikanthan T, Asari KV (2001) Automatic segmentation algorithm for the extraction of lumen region and boundary from endoscopic images. Med Biol Eng Comput 39:8–14

    Article  CAS  PubMed  Google Scholar 

  32. Yan P, Zhou X, Shah M, Wong ST (2008) Automatic segmentation of high-throughput RNAi fluorescent cellular images. IEEE Trans Inf Technol Biomed 12:109–117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2013R1A1A4A01006895) and the Ministry of Science, ICT, and Future Planning (NRF-2013R1A2A2A01068137).

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Authors and Affiliations

  1. Department of Medical IT Engineering, College of Medical Sciences, Soonchunhyang University, Asan City, Chungnam, Korea

    Onseok Lee

  2. Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Korea University College of Medicine, Seoul, Korea

    See Hyun Lee, Sang Hoon Jeong, Hwa Jung Ryu & Sang Wook Son

  3. Division of the Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea

    See Hyun Lee, Sang Hoon Jeong, Hwa Jung Ryu & Sang Wook Son

  4. Research Institute for Skin Image, Korea University College of Medicine, Seoul, Korea

    Jaeyoung Kim, Chilhwan Oh & Sang Wook Son

  5. Department of Dermatology, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, 136-705, Korea

    Sang Wook Son

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  1. Onseok Lee
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Correspondence to Sang Wook Son.

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Lee, O., Lee, S.H., Jeong, S.H. et al. A quantitative study of nanoparticle skin penetration with interactive segmentation. Med Biol Eng Comput 54, 1469–1479 (2016). https://doi.org/10.1007/s11517-015-1405-5

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  • DOI: https://doi.org/10.1007/s11517-015-1405-5

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