The production and use of nanoparticles (NPs) is increasing all over the world and the wide applications of new nanocompounds will cause exposure to many people in the future. The manufacture and manipulation of monodispersed metallic and magnetic nanoparticles (NPs) are increasing for application in textile, disinfectans, magnetic resonance imaging, separation of different catalytic solids, fuel cells, and catalyses¹. People using materials containing NPs  can be exposed  through respiratory, cutaneous and gastrointestinal routes but there is a lack of information about the effects on humans. Skin was regarded as less relevant for NPs absorption but NPs can contaminate the skin and the surfaces of occupationally exposed people and utilizers (NPs can be present in varnishes, surface coating, would dressing, textiles, as well as in cosmetics and creams). There are few data on cosmetics containing nanoTiO₂ but there is a lack of information about the absorption and local or systemic effects associated with skin exposure to metal NPs.

NPs, due to their small size (lower than 100 nm), can penetrate into the body in an easy way through the skin using transappendageal route and gaining local lymph nodes potentially via skin macrophages and Langerhans cells² . Metal NPs can also pass directly through the skin or can release ions that penetrate the skin reaching epidermis and derma. Because of their very small dimensions, NPs can be absorbed by the skin in a higher amount than ordinary metals,  causing local effects (e.g sensitization for sensitizing agents) or systemic effects if NPs enter blood circulation.

What we know and what we do not know about NPs skin absorption

Vogt et al.³ showed that 40 nm nanoparticles are able to penetrate the perifollicular dermis through the hair follicles. Recently, Adami et al. ⁴ confirmed that also metal NPs (gold) can penetrate the skin using hair follicles by using Electra and ESRF synchrotron light . This route can determine a fast penetration of NPs that can reach the deepest layers of the skin.  

In vitro and in vivo studies demonstrated that TiO₂ NPs cannot penetrate the skin when included in cosmetics used for sunprotection⁵ confirming the safety use for consumers, but it has been found that skin damage⁶ or mechanical flexions⁷ can cause an increase of NPs skin penetration.

Baroli et al.⁸ showed that iron nanoparticles are able to penetrate the skin through the stratum corneum lipidic matrix and hair follicle orifices, reaching the deepest layers of the stratum corneoum and less often the uppermost strata of the viable epidermis, although these NPs did not permeate the skin. 

Larese et al.^{6, 9} demonstrated that  gold and silver NPs can penetrate the human skin using in vitro Franz cells. No difference was found between intact and damaged skin for gold NP absorption, while Ag NP  absorption increased up to ten times when the skin was damaged. The difference in Au vs Ag skin absorption could be explained by the fact that silver, but not gold, can release ions in physiological conditions, so that the absorption can occur only through hair follicles or skin glandes.

It is well known that silver can penetrate through the skin causing argyrosis when wound dressing are applied on great surface of damaged skin. Moreover, silver coated textiles are used for atopic patients because of silver antiseptic properties which should help to avoid infections.

At present, it is not known  whether metal NP can increase the risk of sensitization for metals such as Co or Ni and there are no information about the possible adverse health effects in workers employed in the nanotechnology industry. Long-term clinical or epidemiological studies on humans are needed to better understand whether NPs skin contact can cause skin or systemic effects.

Conclusions

Available experimental data suggest that metal NP can permeate the skin depending on the the chemical characteristic of  NP, their size and coating and skin conditions. Skin damage increases significantly metal penetration, suggesting the implementation of preventative measures for people or workers with skin diseases.. It is known that metal NPs present greater surface than bulk material: this  can increase ion release and penetration into the skin not only as NP but also as ions. The shortage of clinical data about new types of NP, such as metals, claims for more studies to improve our understanding about NP skin absorption.

References

¹  Crosera, M., Bovenzi, M., Maina, G., Adami,G., Zanette, C., Florio, C., Larese Filon, F. (2009). Nanoparticle dermal absorption and toxicity: A review of the literature. Int. Arch. Occup. Environ. Health 82, 1043-1055.

² Meidan, V.M., Bonner, M.C., Michniak, B.B. 2005. Transfollicular drug delivery – is it a reality? Int. J. Pharm. 306: 1-14.

³Vogt, A., Combadiere, B., Hadam, S., Stieler, K.M., Lademann, J., Schaefer, H.(2006). 40 nm, but not 750 or 1500 nm, nanoparticles enter epidermal CD1a + cells after transcutaneous application on human skin. J. Invest. Dermatol. 126: 1316 1322.

⁴ Adami, G., Crosera, M., Ceccone, G., Larsson, E., Tromba, G., Brochard, T., Bravin, A., Bovenzi, M., Filon Larese, F. (2011) Skin penetration of gold nanoparticles: a new analytical approach using the synchrotron radiation computed microtomography. XXIV Congresso Nazionale della Società Chimica Italiana Lecce 11-16 settembre 2011.

⁵Gamer, A. O., Leibold, E., and van Ravenzwaay, B. (2006). The in vitro absorption of microfine zinc oxide and titanium dioxide through porcine skin.  Toxicol. in Vitro 20, 301–307.

⁶Larese Filon, F., D’Agostin, F., Bovenzi, M., Crosera, M., Adami, G.  and Maina, G. (2009).     

 Human skin penetration of silver nanoparticles through intact and damaged skin.  Toxicol. 255, 33-37.

⁷Rouse, J. G., Yang, J., Ryman-Rasmussen, J. P., Barron, A. R., and Monteiro-Riviere, N. A. (2007). Effects of mechanical flexion on the penetration of fullerene amino acid-derivatized peptide nanoparticles through skin.  Nano Lett. 7, 155-160.

⁸Baroli, B., Ennas, M. G., Loffredo, F., Isola, M., Pinna, R., and Lopez-Quintela, A. (2007). Penetration of metallic nanoparticles in human full-thickness skin.  J. Invest. Dermatol. 127, 1701–1712.

⁹Larese Filon, F., Crosera, M., Adami, G., Bovenzi, M., Rossi, F., and Maina, G. (2011). Human skin penetration of gold nanoparticles through intact and damaged skin.  Nanotoxicology, Early online 1-9 DOI 10.3109/ 1743390. 2010.551428.