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Nanotechnology and Skin Delivery: Infinitely Small or Infinite Possibilities?
By: Johann W. Wiechers, PhD, JW Solutions
Posted: December 19, 2008, from the January 2009 issue of Cosmetics & Toiletries.
- Figure 1. Theoretical predictions of particle penetration
- Figure 2. Histological sections demonstrating the penetration depth
- Figure 3. Kinetics of the storage of nanoparticles
- Figure 4.The effect of particle size on the UV attenuating properties of titanium dioxide.
- Figure 5. Schematic representation of the size-dependent occlusive effect of lipid nanoparticles
- Figure 6: Cumulative amount of ketorolac
page 8 of 13
The fourth study used titanium dioxide coated with dimethicone or silicone dioxide, 30-60 nm, and zinc oxide (uncoated, < 160 nm) in combination with in vitro pig skin and found no penetration beyond the stratum corneum, yet recoveries in the receptor fluid were 0.8-1.4% of the applied dose.25
When discussing these papers, Nohynek et al.21 state the following: "Similarly, as shown in recent in vitro percutaneous penetration studies, ZnO nanoparticles showed negligible penetration into pig25 and human skin.24 These findings confirmed the results of a number of in vitro or in vivo percutaneous penetration studies on ZnO particles that were reviewed in the opinion from the Scientific Committee on Cosmetic Products and Non-Food Products (SCCNFP).23 None of these studies suggested significant penetration into or through living human or animal skin."
The reason for the increased zinc levels in the third paper, for instance, was the slight dissolution of the zinc oxide particles with subsequent penetration of the zinc ion.24 Because the first and second studies also measured zinc ion levels, this may also have been the case in the studies of the third paper, and therefore not be evidence of zinc oxide nanoparticle penetration. Nohynek et al. thus concluded that "most available theoretical and experimental evidence suggests that insoluble nanoparticles do not penetrate into or through normal as well as compromised human skin,"21--a conclusion with which this author agrees.
Are there therefore no concerns whatsoever regarding topical application of nano-sized components? The only papers describing skin penetration of nanomaterials into the living epidermis are from Nancy Monteiro-Riviere's group, which in 2006 suggested that quantum dots may penetrate into the epidermis or dermis of intact porcine skin.26 Quantum dots are nanocrystals that are used for imaging purposes in medical diagnostics and not in cosmetics. An extended discussion of Monteiro-Riviere's work26,27 on skin penetration of quantum dots is available elsewhere.28
Even if quantum dots do penetrate skin, what does this mean for the skin penetration of nanomaterials applied in cosmetic products? Reading and summarizing this "growing body of (experimental) evidence" already cited10,17,18,26,27 it can be concluded that the systemic exposure of humans following topical application to nanomaterials is very low but not necessarily zero. The highest skin penetration of nanoparticles can be achieved when nanoparticles with particle sizes below 10 nm are used under massage (or flexing) on rodent skin under in vitro conditions.