A sunblock based on bioadhesive nanoparticles

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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).


  1. 1

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

  2. 2

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

  3. 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).

  4. 4

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

  5. 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).

  6. 6

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

  7. 7

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

  8. 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).

  9. 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).

  10. 10

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

  11. 11

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

  12. 12

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

  13. 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).

  14. 14

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

  15. 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).

  16. 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).

  17. 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).

  18. 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).

  19. 19

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

  20. 20

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

  21. 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).

  22. 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).

  23. 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).

  24. 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).

  25. 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).

  26. 26

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

  27. 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).

  28. 28

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

  29. 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).

  30. 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).

  31. 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).

  32. 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).

  33. 33

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

  34. 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).

  35. 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).

  36. 36

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

  37. 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).

  38. 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).

  39. 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).

  40. 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).

  41. 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).

  42. 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).

  43. 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).

  44. 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).

  45. 45

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

  46. 46

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

  47. 47

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

  48. 48

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

  49. 49

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

  50. 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).

  51. 51

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

  52. 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).

  53. 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).

  54. 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).

  55. 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).

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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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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.

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) doi:10.1038/nmat4422

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