Analyzing the Biological Entity of Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 85

silica nanoparticles in water to fully characterize the nanomaterials. To simulate
what is going on in GIT, the food matrices were passed through an in vitro diges-
tion model, which is built of three individual steps: artificial saliva (simulating the
mouth), artificial gastric fluid (simulating the stomach), and artificial intestine fluid
containing duodenal juice and bile juice (simulating the intestine). Basically these
artificial juices are made of different salts mimicking the natural salt concentration
inside these compartments and contain organic compounds that are typical for the
respective compartment. The saliva has a pH of 6.8 and contains urea to simulate
denaturation as well as amylase and mucins. The gastric juice has a pH of 1.3 and
contains pepsin. The duodenal juice has a pH of 8.1 and contains pancreatin and
lipase, whereas the bile juice has a similar pH and contains bile. Thus, these juices
might very well simulate what is likely to happen in vivo . The food matrix is first
dispersed in saliva, then passed over into the gastric fluid but still containing the
saliva, and finally passed into intestinal fluid carrying on saliva and gastric fluid. The
results showed that in all cases the food matrices contained 5%-40% silica nanopar-
ticles in the size range of 5-200 nm when dispersed in saliva. However, in some of
the food matrices such as coffee or instant soup those nanoparticles disappear under
gastric digestion simulation at low pH and they reappear when the pH is neutralized
again during simulation of intestine. Under intestinal conditions the nanoparticles
are even present at a higher percentage compared to the start of the study in saliva
(80% intestinal compared to 5%-40% saliva) and they also appear bigger in size
indicating agglomeration. Taken together this demonstrates that nanoparticles might
undergo a partial or complete dissolution and reformation when passing through the
GIT. Thus it is unlikely that the particles after passing through the GIT will be the
same as applied actually in all aspects, namely they may change chemical composi-
tion, size, and size distribution as well as surface.
Liu and coworkers performed a similar study using nano-silver (Liu et al. 2012).
They could show that nano-silver is prone to oxidative dissolution in the GIT. Ionic
silver may then interact with thiols and the resulting silver-biocomplexes may later
on be photo-decomposed to inorganic Ag 2 S nanoparticles. Interestingly selenide
may rapidly displace sulfur leading to a selenide surface of these particles. Actually
the authors then conclude the implications of these in vitro results for the situa-
tion in vivo . Nano-silver may completely dissolve upon oral uptake and may then
be transported inside the human body as silver-thiol complexes. Later on, in skin,
out of these silver biocomplexes nanoparticles can be reformed by photochemical
reactions. In addition, those newly formed nanoparticles may be further distributed
within the body. But actually the particles that are reformed will not be the same
nanoparticles as before and will contain an altered chemical composition, size, and
size distribution as well as surface. Both studies have important implications for in
vitro testing of nanoparticles that should mimic oral uptake.
4.4.3 C onClusions and C onsiderations for f uture s tudies
There are several lines of evidence that changes occurring within the GIT are really
fundamentally different from what can be observed in plasma or in lungs. Obviously
the major issues inside GIT are not agglomeration/de-agglomeration or adsorption of