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A sunblock based on bioadhesive nanoparticles

Nature Materials volume 14, pages 1278–1285 (2015)Cite this article

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Abstract

The majority of commercial sunblock preparations use organic or inorganic ultraviolet (UV) filters. Despite protecting against cutaneous phototoxicity, direct cellular exposure to UV filters has raised a variety of health concerns. Here, we show that the encapsulation of padimate O (PO)—a model UV filter—in bioadhesive nanoparticles (BNPs) prevents epidermal cellular exposure to UV filters while enhancing UV protection. BNPs are readily suspended in water, facilitate adherence to the stratum corneum without subsequent intra-epidermal or follicular penetration, and their interaction with skin is water resistant yet the particles can be removed via active towel drying. Although the sunblock based on BNPs contained less than 5 wt% of the UV-filter concentration found in commercial standards, the anti-UV effect was comparable when tested in two murine models. Moreover, the BNP-based sunblock significantly reduced double-stranded DNA breaks when compared with a commercial sunscreen formulation.

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Figure 1: Comparison of BNP-based sunscreen and commercial sunscreen.
Figure 2: Evaluation of BNP adhesion.
Figure 3: Synthesis and in vitro evaluation of PO/BNPs.
Figure 4: Histology of dorsal mouse skin sections receiving different topical interventions three days after high dose UV (2,160 J m−2).
Figure 5: CPD staining of mouse dorsal epidermal sheets after receiving different topical interventions and UVB irradiation (160 J m−2).
Figure 6: Staining for γH2AX on mouse dorsal epidermal sheets receiving different topical interventions and UVB irradiation (160 J m−2).

References

  1. Federman, D. G., Kirsner, R. S. & Concato, J. Sunscreen counseling by US physicians. J. Am. Med. Assoc. 312, 87–88 (2014).

    CAS  Google Scholar 

  2. Stern, R. S. The risk of melanoma in association with long-term exposure to PUVA. J. Am. Acad. Dermatol. 44, 755–761 (2001).

    CAS  Google Scholar 

  3. Lim, J. L. & Stern, R. S. High levels of ultraviolet B exposure increase the risk of non-melanoma skin cancer in psoralen and ultraviolet A-treated patients. J. Invest. Dermatol. 124, 505–513 (2005).

    CAS  Google Scholar 

  4. Bordeaux, J. S., Lu, K. Q. & Cooper, K. D. Melanoma: Prevention and early detection. Semin. Oncol. 34, 460–466 (2007).

    Google Scholar 

  5. Liu, H., Tuchinda, P., Fishelevich, R., Harberts, E. & Gaspari, A. A. Human in vitro skin organ culture as a model system for evaluating DNA repair. J. Dermatol. Sci. 74, 236–241 (2014).

    CAS  Google Scholar 

  6. Eller, M. S., Asarch, A. & Gilchrest, B. A. Photoprotection in human skin—a multifaceted SOS response. Photochem. Photobiol. 84, 339–349 (2008).

    CAS  Google Scholar 

  7. Gilchrest, B. A. Photoaging. J. Invest. Dermatol. 133, E2–E6 (2013).

    Google Scholar 

  8. Hanson, K. M., Gratton, E. & Bardeen, C. J. Sunscreen enhancement of UV-induced reactive oxygen species in the skin. Free Radical Biol. Med. 41, 1205–1212 (2006).

    CAS  Google Scholar 

  9. Rass, K. & Reichrath, J. UV damage and DNA repair in malignant melanoma and nonmelanoma skin cancer. Adv. Exp. Med. Biol. 624, 162–178 (2008).

    CAS  Google Scholar 

  10. Gordon Spratt, E. A. & Carucci, J. A. Skin cancer in immunosuppressed patients. Facial Plast. Surg. 29, 402–410 (2013).

    CAS  Google Scholar 

  11. Schwarz, T. & Luger, T. A. Effect of UV irradiation on epidermal cell cytokine production. J. Photochem. Photobiol. B 4, 1–13 (1989).

    CAS  Google Scholar 

  12. Armstrong, B. K. & Kricker, A. The epidemiology of UV induced skin cancer. J. Photochem. Photobiology. B 63, 8–18 (2001).

    CAS  Google Scholar 

  13. Hayden, C. G., Cross, S. E., Anderson, C., Saunders, N. A. & Roberts, M. S. Sunscreen penetration of human skin and related keratinocyte toxicity after topical application. Skin Pharmacol. Physiol. 18, 170–174 (2005).

    CAS  Google Scholar 

  14. Quatrano, N. A. & Dinulos, J. G. Current principles of sunscreen use in children. Curr. Opin. Pediatr. 25, 122–129 (2013).

    CAS  Google Scholar 

  15. Liu, X. et al. Hair follicles contribute significantly to penetration through human skin only at times soon after application as a solvent deposited solid in man. Br. J. Clin. Pharmacol. 72, 768–774 (2011).

    CAS  Google Scholar 

  16. Gulston, M. & Knowland, J. Illumination of human keratinocytes in the presence of the sunscreen ingredient Padimate-O and through an SPF-15 sunscreen reduces direct photodamage to DNA but increases strand breaks. Mutat. Res. 444, 49–60 (1999).

    CAS  Google Scholar 

  17. Bastien, N., Millau, J. F., Rouabhia, M., Davies, R. J. & Drouin, R. The sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid photosensitizes the formation of oxidized guanines in cellulo after UV-A or UV-B exposure. J. Invest. Dermatol. 130, 2463–2471 (2010).

    CAS  Google Scholar 

  18. Krause, M. et al. Sunscreens: Are they beneficial for health? An overview of endocrine disrupting properties of UV-filters. Int. J. Androl. 35, 424–436 (2012).

    CAS  Google Scholar 

  19. Hayden, C. G. J., Roberts, M. S. & Benson, H. A. E. Systemic absorption of sunscreen after topical application. Lancet 350, 863–864 (1997).

    CAS  Google Scholar 

  20. Barnard, A. S. One-to-one comparison of sunscreen efficacy, aesthetics and potential nanotoxicity. Nature Nanotech. 5, 271–274 (2010).

    CAS  Google Scholar 

  21. Leite-Silva, V. R. et al. The effect of formulation on the penetration of coated and uncoated zinc oxide nanoparticles into the viable epidermis of human skin in vivo. Eur. J. Pharm. Biopharm. 84, 297–308 (2013).

    CAS  Google Scholar 

  22. Pan, Z. et al. Adverse effects of titanium dioxide nanoparticles on human dermal fibroblasts and how to protect cells. Small 5, 511–520 (2009).

    CAS  Google Scholar 

  23. Trouiller, B., Reliene, R., Westbrook, A., Solaimani, P. & Schiestl, R. H. Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice. Cancer Res. 69, 8784–8789 (2009).

    CAS  Google Scholar 

  24. Wu, J. et al. Toxicity and penetration of TiO2 nanoparticles in hairless mice and porcine skin after subchronic dermal exposure. Toxicol. Lett. 191, 1–8 (2009).

    CAS  Google Scholar 

  25. Zhang, H., Shan, Y. & Dong, L. A comparison of TiO2 and ZnO nanoparticles as photosensitizers in photodynamic therapy for cancer. J. Biomed. Nanotech. 10, 1450–1457 (2014).

    CAS  Google Scholar 

  26. Planta, M. B. Sunscreen and melanoma: Is our prevention message correct? J. Am. Board Fam. Med. 24, 735–739 (2011).

    Google Scholar 

  27. Lindqvist, P. G. et al. Avoidance of sun exposure is a risk factor for all-cause mortality: Results from the Melanoma in Southern Sweden cohort. J. Intern. Med. 276, 77–86 (2014).

    CAS  Google Scholar 

  28. Plourde, E. Sunscreens—Biohazard: Treat As Hazardous Waste (New Voice Publications, 2011).

    Google Scholar 

  29. Kimura, E., Kawano, Y., Todo, H., Ikarashi, Y. & Sugibayashi, K. Measurement of skin permeation/penetration of nanoparticles for their safety evaluation. Biol. Pharm. Bull. 35, 1476–1486 (2012).

    CAS  Google Scholar 

  30. Vogt, A. et al. 40 nm, but not 750 or 1,500 nm, nanoparticles enter epidermal CD1a + cells after transcutaneous application on human skin. J. Invest. Dermatol. 126, 1316–1322 (2006).

    CAS  Google Scholar 

  31. Mitragotri, S., Burke, P. A. & Langer, R. Overcoming the challenges in administering biopharmaceuticals: Formulation and delivery strategies. Nature Rev. Drug Discov. 13, 655–672 (2014).

    CAS  Google Scholar 

  32. Gu, H. & Roy, K. Topical permeation enhancers efficiently deliver polymer micro and nanoparticles to epidermal Langerhans’ cells. J. Drug Deliv. Sci. Technol. 14, 265–273 (2004).

    CAS  Google Scholar 

  33. Deng, Y. et al. The effect of hyperbranched polyglycerol coatings on drug delivery using degradable polymer nanoparticles. Biomaterials 35, 6595–6602 (2014).

    CAS  Google Scholar 

  34. Thavarajah, R., Mudimbaimannar, V. K., Elizabeth, J., Rao, U. K. & Ranganathan, K. Chemical and physical basics of routine formaldehyde fixation. J. Oral Maxillofac. Pathol. 16, 400–405 (2012).

    Google Scholar 

  35. Sompuram, S. R., Vani, K., Messana, E. & Bogen, S. A. A molecular mechanism of formalin fixation and antigen retrieval. Am. J. Clin. Pathol. 121, 190–199 (2004).

    CAS  Google Scholar 

  36. Zhu, H. et al. Global analysis of protein activities using proteome chips. Science 293, 2101–2105 (2001).

    CAS  Google Scholar 

  37. Artzi, N., Shazly, T., Baker, A. B., Bon, A. & Edelman, E. R. Aldehyde-amine chemistry enables modulated biosealants with tissue-specific adhesion. Adv. Mater. 21, 3399–3403 (2009).

    CAS  Google Scholar 

  38. Gu, F. et al. Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers. Proc. Natl Acad. Sci. USA 105, 2586–2591 (2008).

    CAS  Google Scholar 

  39. Rao, S. S., Han, N. & Winter, J. O. Polylysine-modified PEG-based hydrogels to enhance the neuro-electrode interface. J. Biomater. Sci. Polym. Ed. 22, 611–625 (2011).

    CAS  Google Scholar 

  40. Swindle, M. M., Makin, A., Herron, A. J., Clubb, F. J. & Frazier, K. S. Swine as models in biomedical research and toxicology testing. Vet. Pathol. 49, 344–356 (2012).

    CAS  Google Scholar 

  41. Barbero, A. M. & Frasch, H. F. Pig and guinea pig skin as surrogates for human in vitro penetration studies: A quantitative review. Toxicol. In Vitro 23, 1–13 (2009).

    CAS  Google Scholar 

  42. Downes, A. M., Matoltsy, A. G. & Sweeney, T. M. Rate of turnover of the stratum corneum in hairless mice. J. Invest. Dermatol. 49, 400–405 (1967).

    CAS  Google Scholar 

  43. Nair, H. B., Ford, A., Dick, E. J. Jr, Hill, R. H. Jr & VandeBerg, J. L. Modeling sunscreen-mediated melanoma prevention in the laboratory opossum (Monodelphis domestica). Pigment Cell Melanoma Res. 27, 843–845 (2014).

    Google Scholar 

  44. Bennassar, A., Grimalt, R., Romaguera, C. & Vilaplana, J. Two cases of photocontact allergy to the new sun filter octocrylene. Dermatol. Online J. 15, 14 (2009).

    Google Scholar 

  45. Rietschel, R. L. Fisher’s Contact Dermatitis 6th edn (PMPH-USA, 2007).

    Google Scholar 

  46. Andreas Katsambas, T. L. European Handbook of Dermatological Treatments (Springer, 2003).

    Google Scholar 

  47. Flick, E. W. Cosmetic and Toiletry Formulations (Noyes Publications, 1984).

    Google Scholar 

  48. Tanner, P. R. Sunscreen product formulation. Dermatol. Clin. 24, 53–62 (2006).

    CAS  Google Scholar 

  49. Egerton, T. A. UV-absorption—the primary process in photocatalysis and some practical consequences. Molecules 19, 18192–18214 (2014).

    CAS  Google Scholar 

  50. Perugini, P. et al. Effect of nanoparticle encapsulation on the photostability of the sunscreen agent, 2-ethylhexyl-p-methoxycinnamate. Int. J. Pharm. 246, 37–45 (2002).

    CAS  Google Scholar 

  51. Matsumura, Y. & Ananthaswamy, H. N. Toxic effects of ultraviolet radiation on the skin. Toxicol. Appl. Pharmacol. 195, 298–308 (2004).

    CAS  Google Scholar 

  52. Han, J., Colditz, G. A., Samson, L. D. & Hunter, D. J. Polymorphisms in DNA double-strand break repair genes and skin cancer risk. Cancer Res. 64, 3009–3013 (2004).

    CAS  Google Scholar 

  53. Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S. & Bonner, W. M. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J. Biol. Chem. 273, 5858–5868 (1998).

    CAS  Google Scholar 

  54. Deng, Y., Zhu, X. Y., Kienlen, T. & Guo, A. Transport at the air/water interface is the reason for rings in protein microarrays. J. Am. Chem. Soc. 128, 2768–2769 (2006).

    CAS  Google Scholar 

  55. Deng, Y. et al. Global analysis of human nonreceptor tyrosine kinase specificity using high-density Peptide microarrays. J. Proteome Res. 13, 4339–4346 (2014).

    CAS  Google Scholar 

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Acknowledgements

We are grateful to Y. Wu, Y. Lu, R. Fan, Y. Pan, T. Xu and T. Kyriakides of Yale University for access to their instruments in their laboratories. We thank E. Quijano and T. Kyriakides for helpful discussions and J. Zhang for technical assistance. This work was supported by NIH grants CA102703, EB000487 and CA149128, Yale School of Medicine Office of Student Research, and the Howard Hughes Medical Research Fellowship.

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  1. Yang Deng and Asiri Ediriwickrema: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biomedical Engineering, Yale University, 55 Prospect Street, New Haven, Connecticut 06511, USA

    Yang Deng, Asiri Ediriwickrema, Fan Yang & W. Mark Saltzman

  2. Department of Dermatology, Yale University, 333 Cedar Street, New Haven, Connecticut 06520, USA

    Julia Lewis & Michael Girardi

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  1. Yang Deng
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Contributions

Y.D., A.E., J.L., F.Y., M.G. and W.M.S. designed the experiments. Y.D., A.E., F.Y. and J.L. performed the experiments. All the authors were involved in the analyses and interpretation of data. Y.D., A.E., M.G. and W.M.S. wrote the paper, with the help of the co-authors.

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Correspondence to W. Mark Saltzman.

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Deng, Y., Ediriwickrema, A., Yang, F. et al. A sunblock based on bioadhesive nanoparticles. Nature Mater 14, 1278–1285 (2015). https://doi.org/10.1038/nmat4422

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