Biomedical Engineering Reference
In-Depth Information
particles: 14-nm-diameter latex NPs cross within 2 min, 415 nm particles cross within 30 min, and
1000 nm particles do not pass this barrier (Hoet et al. 2004). Particles that penetrate the mucus layer
reach the enterocytes and are able to translocate further (Hoet et al. 2004). Enterocytes are a type of
epithelial cell of the superficial layer of the small and large intestine tissue that aid in the absorption
of nutrients. When in contact with the submucosal tissue, NPs can enter the lymphatic system and
capillaries, and are then able to reach various organs (Hoet et al. 2004).
Diseases such as diabetes may lead to a higher absorption of particles in the GI tract (Hoet et al.
2004). For example, rats with experimentally induced diabetes had a 100-fold increase in the absorp-
tion of 2 μm polystyrene particles (Hoet et al. 2004) relative to nondiabetic rats. Also, inflammation
may lead to the uptake and translocation of larger particles of up to 20 μm (Ballestri et al. 2001).
The kinetics of particles in the GI tract strongly depends on the charge of the particles, as posi-
tively charged latex particles are trapped in the negatively charged mucus while negatively charged
latex NPs diffused across the mucus layer and became available for interactions with epithelial cells
(Hoet et al. 2004).
13.2.3 t
raNslocatIoN
Varying the characteristics of NPs, such as size, surface charge, attachment of ligands, or surfactant
coatings, offers the possibility for the site-specific targeting of different regions of the GI tract. The
fast transit of materials through the intestinal tract (on the order of hours), together with the continu-
ous renewal of the epithelium, led to the hypothesis that nanomaterials will not remain there for
indefinite periods (Hoet et al. 2004). Most of the studies of ingested NPs have shown that they are
rapidly eliminated (within 48 h) with 98% in the feces and most of the remainder is eliminated via
urine (Oberdörster et al. 2005). However, other studies indicate that certain NPs can translocate to
blood, spleen, liver, bone marrow (Jani et al. 1990), lymph nodes, kidneys, lungs, and brain, and can
also be found in the stomach and small intestine (Rae et al. 2005). The oral uptake of polystyrene
spheres of various sizes (50 nm-3 μm) by rats resulted in a systemic distribution to the liver, spleen,
blood, and bone marrow (Jani et al. 1990).
Particles larger than 100 nm did not reach the bone marrow, while those larger than 300 nm were
absent from the blood (Jani et al. 1990). During this study, no particles were detected in the heart
or lung tissue. Studies using iridium did not show significant uptake, while TiO
2
NPs were found in
the blood and liver (Oberdörster et al. 2005). For several days following the oral inoculation of mice
with a relatively biologically inert nanometer-sized plant virus (cowpea mosaic virus), the virus
was found in a wide variety of tissues throughout the body, including the stomach, small intestine,
lymph nodes, spleen, liver, lung, kidney, brain, and bone marrow (Rae et al. 2005).
The exact order of translocation from the GI tract to organs and blood is not known. However, a
case study of dental prosthesis porcelain debris internalized by intestinal absorption suggests that
the intestinal absorption of particles is followed by their clearance from the liver before they reach
general circulation and the kidneys (Ballestri et al. 2001).
13.2.4
a
dverse
h
ealth
e
ffects
of
gI t
ract
u
ptake
13.2.4.1 Reaction-Reduced Toxicity
There is a complex mix of compounds, enzymes, food, bacteria, and so on, that can interact with
ingested particles and sometimes reduce their toxicity in the intestinal tract (Hoet et al. 2004). It
was reported that particles are less cytotoxic
in vitro
and in a medium with high protein content.
13.2.4.2 Crohn's Disease, Ulcerative Colitis, and Cancer
NPs have been constantly found in the colon tissue of subjects affected by cancer, Crohn's disease,
and ulcerative colitis, while NPs were absent in healthy subjects (Gatti 2004). The NPs present in
diseased subjects had various chemical compositions and were not considered toxic in their bulk
