Tag Archives: AgNO3

Nanoparticles and gut effects – generally recognized as safe?

Models for oral uptake of nanoparticles in consumer products

Titanium dioxide nanoparticle ingestion alters nutrient absorption in an in vitro model of the small intestine

Zhongyuan Guo, Nicole J. Martucci, Fabiola Moreno-Olivas, Elad Tako, Gretchen J. Mahler. Titanium dioxide nanoparticle ingestion alters nutrient absorption in an in vitro model of the small intestine. NanoImpact, 2017; 5: 70 DOI: 10.1016/j.impact.2017.01.002

In the study above, researchers took a meal’s worth of titanium oxide nanoparticles — 30 nanometers across — over four hours (acute exposure), or three meal’s worth over five days (chronic exposure) and determined the effect on the gut. Acute exposure caused no harm,  but chronic exposure diminished the absorptive projections on the surface of intestinal cells called microvilli. With fewer microvilli, the intestinal barrier was weakened, metabolism slowed and some nutrients — iron, zinc, and fatty acids, specifically — were more difficult to absorb. Enzyme functions were negatively affected, while inflammation signals increased. It turns out that nanoparticles are everywhere, especially in food, cosmetics, and pharmaceuticals. It can enter the digestive system through toothpastes, since Titanium dioxide is used to create abrasion needed for cleaning. The oxide is also used in some chocolate to give it a smooth texture; in donuts to provide color; and in skimmed milks for a brighter, more opaque appearance which makes the milk more palatable. Dunkin Donuts stopped using powdered sugar with titanium dioxide nanoparticles in 2015 in response to pressure from the advocacy group As You Sow.


There is emerging evidence that we have generated strategies to utilise nanoparticles for dietary and physiological benefit evolutionarily.  Thus, nanoparticulate structures are neither inherently toxic nor inherently safe: like all molecules these decisions will rest upon molecular structure, biological environment, degree of exposure and host susceptibility.

Nanoparticues act in a number of wasy internally, especially in the gut lumen, where they are exposed to mucin, proteins, pH changes, and other existing charged particles. There has been described a protein coating of nanoparticle surfaces, referred to as a ‘corona’, this phenomenon has been known for decades and will inevitably happen in the particle’s native environment. In the gastrointestinal tract it is likely that the acidic pH of the stomach, which mainly is maintained even postprandially, and the presence of gastrointestinal enzymes, will serve to denude ingested particles of their surface-adsorbed molecules but then re-adsorption of novel entities will occur in the less acidic small bowel lumen.

There are many exogenous inorganic particles are man-made particles comprising titanium dioxide or silicates/aluminosilicates. Titanium dioxide (designated E171 in Europe) is used for whitening and brightening foods, especially for confectionary, white sauces and dressings, and certain powdered foods.

Titanium dioxide (designated E171 in Europe) is used for whitening and brightening foods, especially for confectionary, white sauces and dressings, and certain powdered foods. It is also used in the pharmaceutical industry as an opacity agent. Titanium dioxide is typically found in gut tissue in the anatase polymorphic form and is a 100-200 nm diameter spherical particle that is resistant to gastrointestinal degradation. Particulate silicates and aluminosilicates (E554, E556 and E559 in Europe) are used in the food industry as anti-caking agents and to allow the flow of powders, and some are present in cheeses, sugars and powdered milks. In the UK, the major five food sources of particulate silicates are salt, drinking powders, chewing gum, instant pot savory snacks and icing sugar.Overall, intake of dietary inorganic microparticles in the UK has been estimated to be about 40 mg/person/day (35 mg for the silicates and 5 mg for titanium dioxide) which equates to a staggering daily exposure of 101214 particles/person.

How are  the partciles taken up in the gut? M-cell-uptake (transcytosis) at the surface of intestinal lymphoid aggregates is the quintessential pathway for gut particle uptake and is very well described, especially for large nanoparticles (20-100 nm) and small microparticles (100-500 nm). Hydrophobic particles appear to be much better taken up than hydrophilic particles,  and  generally, small particles are better taken up than large ones with, perhaps, an optimal size of around 50 nm diameter.

Other sources of nanoparticles (NM) relevant for oral exposure comprise mainly cosmetics (sunscreen, lipsticks, skin creams, toothpaste) and food (packaging, storage life sensors, food additives, juice clarifiers). Whereas NMs in food are intended to be ingested, nanoparticles for instance in cosmetics and ingredients in food packaging may accidently get into the gastrointestinal tract. Major materials used in these products are: silver, and metal oxides of zinc, silica, and titanium. Nanosilver (Ag) is used in food packaging. According to the Woodrow Wilson Nanotechnology Consumer Products Inventory 2011, Ag nanoparticles are the most commonly used new NM in consumer products followed by TiO2, ZnO, platinum (Pt) and silicium oxide NMs (http://www.nanotechproject.org/inventories/consumer/). Although gold NMs are also used in cosmetics, food packaging, beverage and toothpaste their main applications are in the medical field.

Decrease of particle size in the nanoscale has been identified as a main parameter for the increased toxicity of different materials. Polystyrene, for instance, is a very biocompatible polymer used in cell culture. Nanoparticles, however, made from this material are cytotoxic.

Compared to other metal and metal oxide nanoparticles intake of TiO2 by food is relatively high at 5 mg TiO2/person/d .Metal and metal oxide nanoparticles can accumulate in plants  and in animals of the food chain. That is worrisome.

A number of factors effect uptake of particles by the gut. Even in healthy individuals gastrointestinal transit is by far not constant and shows considerable variation through the large intestine . These effects are known to influence oral bioavailability of conventional drugs but are even more important for the effects of NMs because NMs readily adsorb proteins. Mucus represents an efficient acellular barrier. Mucus consists of mucin proteins (highly glycosylated extracellular proteins with characteristic gel-forming properties), antiseptic proteins (lysozyme) and other proteins (lactoferrin), inorganic salts and water. The major functions are the protection and the lubrication of the underlying tissue. The saliva, which is produced by the salivary glands, mainly consists of water (up to 99.5%), inorganic salts, proteins, and mucins. The high molecular weight mucin MG1 can bind to the surface of the epithelium and build the so-called mucus layer, displaying the acellular barrier of the oral cavity The mucus of the following parts, stomach and small and large intestine, is mainly produced by intraepithelial cells, and hickness increases from proximal to distal parts of the small and large intestine . Depending on the method used for the determination, the thickness of the mucus layer shows marked variation..The characteristics facilitating the passage through human mucus are relatively well known: electrostatic repulsion from negatively charged sugar moieties favors the penetration of positively charged hydrophilic molecules; the passage of lipophilic compounds is slow. Viruses, like the Norwalk virus with a size of 38 nm and human papilloma virus with a size of 55 nm diffused in human mucus as rapidly as they do in water These findings suggest that the surface charge plays a crucial role in the transport rates of nanoparticles through a mucus layer

In addition to particle size, dose and duration of the exposure are important for the interpretation of the data. In addition to particle size, dose and duration of the exposure are important. There is  a size-dependent decrease of the uptake from 34% for 50 nm particles to 26% for 100 nm particles , and dose and duration of the exposure are also important for absorption and uptake of NM.

Changes in mucus composition induced by Ag nanoparticles (Jeong et al., 2010), polystyrene particles and diesel exhaust increased mucus permeability and permeation of small molecules by a factor of 5. Thus NM enter more quickly through disease barriers.

The adherence of polystyrene nanoparticles to inflamed colonic mucosa was much higher than to normal mucosa. Inflammation appears to increase uptake and permeation of NMs in vitro and in vivo. Inflammation caused by Yersinia pseudotuberculosis increases the uptake of 100 nm carboxyl polystyrene particles in cell monolayers and in intestinal biopsies. Other factors of absorption include pH and thickness of the mucus layer, the gastrointestinal flora and in gastrointestinal passage time (motility)

Whereas plasma membranes restrict the cellular access for metal ions like silver cations, silver nanoparticles were readily internalized and intracellular silver concentrations were much higher than for silver ions. Studies for uptake and toxicity should, therefore, include AgNO3 for silver nanoparticles (Trojan horse effect) or bulk material.. Absorption may also be altered by a changed metabolization by enterocytes. Polystyrene and silver particles have been shown to inhibit the activity of cytochrome P450 enzymes, of note

To avoid foods rich in titanium oxide nanoparticles you should avoid processed foods, and especially candy. This information may make one question if these NM have any impact on the surge of colitis seen ion the general poplulation? How about autoimmune diseases? How about general inflammation, for if NM damage the intestinal barrier, inflammation results and it’s attendant consequences.