The only published technical papers describing skin penetration of nanomaterials into the living epidermis are from the group of Dr. Nancy Monteiro-Riviere in Rayleigh, N. C., USA. In 2006 Ryman-Rasmussen et al.1 published a paper in which it is suggested that quantum dots may penetrate into the epidermis or dermis of intact porcine skin. Quantum dots are nanocrystals that are used for imaging purposes in medical diagnostics (and not in cosmetics). They have a metallic core surrounded by an inorganic shell coating. Organic coatings may be added to the surface of the shell to provide a charge and allow the binding of antibodies so that they have greater biocompatibility, solubility or bind to specific receptors in cells or tissue.
Two types of quantum dots were used in the Ryman-Rasmussen study with three different coatings: spherical shaped quantum dots with a particle size of 4.6 nm and ellipsoid shaped quantum dots with a particle size of 6 nm (minor axis) and 12 nm (major axis). It should be kept in mind that the hydrodynamic diameter of these quantum dots is larger due to solvation effects, especially for the neutral coating.
Confocal microscopy revealed that the smaller, spherical quantum dots penetrated the stratum corneum of freshly dermatomed pig skin and localized within the epidermal and dermal layers by 8 hr irrespective of their surface coating. Similarly, the larger ellipsoid quantum dots with a neutral or cationic coating also localized within the epidermal layers by 8 hr. No penetration of the larger quantum dots with the anionic coating was evident until 24 hr, at which time localization in the epidermal layers was observed.
The authors concluded that quantum dots of different sizes, shapes, and surface coatings can penetrate intact skin at an occupationally relevant dose within the span of an average-length work day, suggesting that “skin is surprisingly permeable to nanomaterials with diverse physicochemical properties and may serve as a portal of entry for localized, and possibly systemic, exposure of humans to quantum dots and other nanoscale materials.”1 Is this the “growing body of evidence” that our friends at Friends of the Earth are referring to when they allege the toxicity of nanomaterials for humans and the environment?
Nohynek et al.2 warn us that these studies were conducted with the quantum dots being applied in quite alkaline solutions (pH 8.3 or 9.0), but evidence for increased skin penetration at this pH is limited. In 1965, Bettley already did not find a correlation of permeation with pH,3 whereas a much more recent paper by Sznitowska et al.4 reaches a similar conclusion: up to pH 11.0, no change in the penetration of hydrocortisone and testosterone was found.
It is, therefore, interesting to read a later paper on quantum dot penetration from the same group.5 Again, they used both the small spherical and the larger ellipsoid quantum dots but only with the anionic coating that—in the previous study—localized mainly in the epidermis by 8 hr (small spherical quantum dots) or did not penetrate until 24 hr (larger ellipsoid quantum dots). The objective of the new study was to investigate whether flexion, tape stripping and abrasion could cause an increase in the penetration of quantum dots of different sizes and shapes.
Using rat skin instead of pig skin (as used in the first study), it was found that on intact skin the skin penetration of both quantum dots was primarily limited to the uppermost stratum corneum layers. Barrier perturbation by tape stripping did not cause penetration, but abrasion with sandpaper allowed the quantum dots to penetrate deeper into the dermal layers. As a result, quantum dot penetration not only depends on nanoparticle size and charge, but also on species differences in the skin and hair follicle density. Occasionally, retention of quantum dots was observed in the hair follicles in abraded skin.
Penetration of nanoparticles not only occurs on the surface of the stratum corneum layers or within the stratum corneum layers; these particles may also penetrate further down the skin with skin flexing.5 These findings are in full agreement with the influence of massage as described in this author’s column in the January issue of Cosmetics & Toiletries magazine.
1. JP Ryman-Rasmussen, JE Riviere and NA Monteiro-Riviere, Penetration of intact skin by quantum dots with diverse physicochemical properties, Toxicol Sci 91 159–165 (2006)
2. GJ Nohynek, J Lademann, C Ribaud and MS Roberts, Grey goo on the skin? Nanotechnology, cosmetic and sunscreen safety, Crit Rev Toxicol 37 251–277 (2007)
3. FR Bettley, The influence of detergents and surfactants on epidermal permeability, Br J Dermatol 77 98–100 (1965)
4. M Sznitowska, S Janicki and A Baczek, Studies on the effect of pH on the lipoidal route of penetration across stratum corneum, J Control Rel 76 327–335 (2001)
5. LW Zhang and NA Monteiro-Riviere, Assessment of quantum dot penetration into intact, tape-stripped, abraded and flexed rat skin, Skin Pharmacol Physiol 21 166–180