For a mini-review published in the journal Particle and Fibre Technology in 2021, scientists wanted to evaluate whether Ti02 particles contributed to the development and/or exacerbation of irritable bowel disease, and whether they altered the four elements of intestinal barrier function: the intestinal microbiota, the immune system, the mucus layer, and the epithelium. The breakdown of these four elements can contribute to autoimmune, neurological, inflammatory, infectious, and metabolic diseases. Following their review, the researchers concluded: “Data indicate that TiO2 is able to alter the four compartments of IBF and to induce a low-grade intestinal inflammation associated or not with pre-neoplastic lesions.” 

Materials

When it comes to sourcing titanium dioxide, it is essential to understand the various processes involved in its production. The two primary production methods are the sulfate process and the chloride process. The sulfate process tends to be more cost-effective in certain contexts, but it also generates a substantial amount of waste, putting pressure on manufacturers to invest in waste treatment technologies. On the other hand, the chloride process is known for its superior quality and lower environmental impact, albeit at a higher production cost.

Different dermal cell types have been reported to differ in their sensitivity to nano-sized TiO₂ . Kiss et al. exposed human keratinocytes (HaCaT), human dermal fibroblast cells, sebaceous gland cells (SZ95) and primary human melanocytes to 9 nm-sized TiO₂ particles at concentrations from 0.15 to 15 μg/cm² for up to 4 days. The particles were detected in the cytoplasm and perinuclear region in fibroblasts and melanocytes, but not in kerati-nocytes or sebaceous cells. The uptake was associated with an increase in the intracellular Ca²⁺ concentration. A dose- and time-dependent decrease in cell proliferation was evident in all cell types, whereas in fibroblasts an increase in cell death via apoptosis has also been observed. Anatase TiO₂ in 20–100 nm-sized form has been shown to be cytotoxic in mouse L929 fibroblasts. The decrease in cell viability was associated with an increase in the production of ROS and the depletion of glutathione. The particles were internalized and detected within lysosomes. In human keratinocytes exposed for 24 h to non-illuminated, 7 nm-sized anatase TiO_2, a cluster analysis of the gene expression revealed that genes involved in the “inflammatory response” and “cell adhesion”, but not those involved in “oxidative stress” and “apoptosis”, were up-regulated. The results suggest that non-illuminated TiO₂ particles have no significant impact on ROS-associated oxidative damage, but affect the cell-matrix adhesion in keratinocytes in extracellular matrix remodelling. In human keratinocytes, Kocbek et al. investigated the adverse effects of 25 nm-sized anatase TiO₂ (5 and 10 μg/ml) after 3 months of exposure and found no changes in the cell growth and morphology, mitochondrial function and cell cycle distribution. The only change was a larger number of nanotubular intracellular connections in TiO₂-exposed cells compared to non-exposed cells. Although the authors proposed that this change may indicate a cellular transformation, the significance of this finding is not clear. On the other hand, Dunford et al. studied the genotoxicity of UV-irradiated TiO₂ extracted from sunscreen lotions, and reported severe damage to plasmid and nuclear DNA in human fibroblasts. Manitol (antioxidant) prevented DNA damage, implying that the genotoxicity was mediated by ROS.

Asia-Pacific accounted for the largest revenue share in 2019. China and India are the key markets in the region that have a growing paint and plastics industry, owing to rise in urbanization and industrial developments such as in automotive and construction domains. 

Fig. 9. Selected images of damaged skin treated with P25TiO₂NPs 10% (left) and healthy skin treated with VitaminB2@P25TiO₂NPs 10% (right).