The aim of this work was to examine particularly the Degussa P25 titanium dioxide nanoparticles (P25TiO₂NPs) because they are among the most employed ones in cosmetics. In fact, all kinds of titanium dioxide nanoparticles (TiO₂NPs) have gained widespread commercialization over recent decades. This white pigment (TiO₂NPs) is used in a broad range of applications, including food, personal care products (toothpaste, lotions, sunscreens, face creams), drugs, plastics, ceramics, and paints. The original source is abundant in Earth as a chemically inert amphoteric oxide, which is thermally stable, corrosion-resistant, and water-insoluble. This oxide is found in three different forms: rutile (the most stable and substantial form), brookite (rhombohedral), and anatase (tetragonal as rutile), of these, both rutile and anatase are of significant commercial importance in a wide range of applications [3]. Additionally, the nano-sized oxide exhibits interesting physical properties, one of them is the ability to act as semiconducting material under UV exposure. In fact, TiO₂NPs are the most well-known and useful photocatalytic material, because of their relatively low price and photo-stability [4]. Although, this photoactivity could also cause undesired molecular damage in biological tissues and needs to be urgently assessed, due to their worldwide use. However, not all nanosized titanium dioxide have the same behavior. In 2007, Rampaul A and Parkin I questioned: “whether the anatase/rutile crystal form of titanium dioxide with an organosilane or dimethicone coat, a common titania type identified in sunscreens, is appropriate to use in sunscreen lotions” [5]. They also suggested that with further study, other types of functionalized titanium dioxide could potentially be safer alternatives. Later, Damiani found that the anatase form of TiO₂NPs was the more photoactive one, and stated that it should be avoided for sunscreen formulations, in agreement with Barker and Branch (2008) [6,7].

Both P25TiO₂NPs (with or without vitamin B2) were not found beyond the epidermis in 99% of the analyzed TEM images (Fig. 8). This is coherent with previous findings showing that nanoparticles greater than 50 nm can not penetrate the skin, even in vivo models with movement, stretching, and friction [54]. However, in one of the zones, a few nanoparticles were observed inside a hair follicle. This could be due to the follicle exposure after the localized rupture of this physical barrier when rats were shaved in order to clean the area for cream topical administration. This finding suggests that nanoparticle-based sunscreen should not be applied on recently shaved or harmed skin, in order to avoid nanoparticle skin penetration.