Investigation of micronized titanium dioxide penetration in human skin xenografts and its effect on cellular functions of human skin‐derived cells

Abstract

Titanium dioxide (TiO2) nanoparticles are ubiquitously used materials in everyday life (e.g. paints,household products and plastic goods). However, despite the wide array of common applications, their pathogenetic role was also suggested under certain conditions (e.g. pulmonary neoplasias and lung fibrosis). From a dermatological point of view, it is also of great importance that TiO2 also serves as a physical photoprotective agent in sunscreens and is widely used in various cosmetic products. However, the effect of TiO2 on human cutaneous functions is still unknown. Therefore, in the current study, we investigated the in vivo penetration of TiO2 via human skin transplanted to immunodeficient mice and,furthermore, we measured the in vitro effects of nanoparticles on various functional properties of numerous epidermal and dermal cells in culture. Hereby, using various nuclear microscopy methods, we provide the first evidence that TiO2nanoparticles in vivo do not penetrate through the intact epidermal barrier. However, we also report that TiO2, when exposed directly to cell cultures in vitro, exerts significant and cell-type dependent effects on such cellular functions as viability, proliferation, apoptosis and differentiation. Therefore, our novel findings will hopefully inspire one to systemically explore in future, clinically oriented trials whether there is indeed a risk from micronized TiO2-containing products on skin with an impaired stratum corneum barrier function.

In vitro and in vivo toxicity assessment of nanoparticles

“…Similarly, when human bronchial epithelial cells were treated with zinc oxide at 100 μg/mL, the observed effects include the release of LDH, decrease in cell viability and oxidative stress [219]. The toxicity of titanium nanoparticles affects differentiation, cell proliferation, apoptosis and mobility [220,221]. The toxicity of the titanium oxide nanoparticle was observed when keratinocyte cell line (HaCaT), human dermal fibroblasts and human immortalized sebaceous gland cell lines (SZ95) were used.…”

“…The toxicity of the titanium oxide nanoparticle was observed when keratinocyte cell line (HaCaT), human dermal fibroblasts and human immortalized sebaceous gland cell lines (SZ95) were used. The cytotoxicity affected cellular functions including differentiation, cell proliferation and mobility which resulted in apoptosis [220].Upregulation of fibrogenic mediators including IL-4, IL-10 and IL-13 was also observed contributing to fibrotic changes [195].…”

Toxicity Associated with the Photo Catalytic and Photo Stable Forms of Titanium Dioxide Nanoparticles Used in Sunscreen lotion

“…195 Overall, the weight of scientific evidence suggests that insoluble nanoparticles used in sunscreens pose no or negligible risk to human health 196,197,[201][202][203][204][205][206][207][208][209][210] however there are some discrepancies in the results probably related to differences in techniques and methods, laboratory conditions, and the absence of standardized evaluation protocols.…”

“…3,[195][196][197][198][199][200] Skin exposure to nano particle-containing sunscreens leads to incorporation of TiO 2 and ZnO in the stratum corneum, which may alter certain properties due to particle-particle, particle-skin, and skin-particle-light physicochemical interactions. 195 Overall, the weight of scientific evidence suggests that insoluble nanoparticles used in sunscreens pose no or negligible risk to human health 196,197,[201][202][203][204][205][206][207][208][209][210] however there are some discrepancies in the results probably related to differences in techniques and methods, laboratory conditions, and the absence of standardized evaluation protocols.The reason for these results is unclear based on the observation that most other nano particle types (polymers, metals and carbon nano tubes) permeate the skin. The answer may be that it is possible that the particle agglomeration, 211,212 when combined with the particles' intrinsic hydrophobicity, allows particles to become trapped in the lipid lamella and remain until desquamation or sebaceous secretion removes them from follicles.…”

Inorganic UV filters

“…The organic UV filters are usually aromatic compounds with a carbonyl group. On receiving the energy of UV photons, the organic UV filters can act in three ways: (i) undergo conformational molecular changes, (ii) emit radiation at higher wavelength or (iii) release incident energy as heat (Antoniou et al, 2008;Kiss et al, 2008). The action mode of the organic protector molecules is reversible, so that the same molecule can function repeatedly.…”