Biomedical Engineering Reference
In-Depth Information
materials occurs during ingestion. The entire cascade of events together with absorption, distribu-
tion, metabolism, and excretion/elimination occur following ingestion and determine the internal
exposure and toxicity of these substances. Nevertheless, due to the interactions of nanomaterials
with the surrounding matrix and unexpected effects resulting from this, little is known regarding
the behavior and fate of nanomaterials in the GI tract (EFSA 2009).
13.4.1 gI a BsorptIoN of Np s
NPs can be distributed to the same organ by several routes of exposure. For example, NPs found
in the GI tract can originate from ingested products. Alternatively, they can also reach the GI tract
via an indirect route. For example, particles can be absorbed in systemic circulation via the respira-
tory tract or skin. From there, particles can be distributed to the liver, taken up by hepatocytes, and
excreted in bile to the GI tract.
In this section, the absorption of NPs into the human body via different exposure pathways such
as inhalation, oral, skin, and parenteral is addressed. In pharmacokinetics, absorption represents the
process by which unchanged compounds (e.g., NPs) proceed from the site of administration to the
central blood circulation (site of measurement) (Werner et al. 2007).
The GI tract may represent an important port of entry for NPs since food products may eventu-
ally contain NPs (Lomer et al. 2002; Maynard and Michelson 2005). In addition, inhaled particles
can be excreted via the mucociliary escalator and can be subsequently ingested into the GI tract.
The contribution of the oral exposure following inhalation depends on the particles' physicochemi-
cal characteristics and size. The computer-based multiple-path particle dosimetry model (Price
et al. 2002) can predict the amount of poorly soluble, nontoxic, solid NPs (10 nm and larger) trans-
ported from the lungs to the GI tract in rats. A validated extrapolation to the human situation is not
possible yet.
Micronized particles can enter the body by a process called persorption, the paracellular uptake of
particles from the GI tract into lymphatic and blood circulation (Volkheimer et al. 1968; Volkheimer
1974). Several studies in rats have shown that nano- and microsized particles (50 nm-20 μm) are
mainly absorbed through Peyer's patches of the small intestine, while Peyer's patches only comprise
a small percentage of the total surface of the small intestine. In addition, absorption via intesti-
nal enterocytes has been demonstrated (Carr et al. 1996; Florence 2005; Hillery et al. 1994; Jani
et al. 1990). Charge appears to be an important determinant of the extent of absorption. Positively
charged particles seem to be absorbed more effectively through the GI tract than neutral and nega-
tively charged particles (Florence 1997, 2005; Hussain et al. 2001; Janes et al. 2001). Additionally,
the size of the particles determines the extent of absorption. Polystyrene NPs of 50 and 100 nm were
found to be absorbed to the extent of 34% and 26%, respectively (Jani et al. 1990). The efficiency
in absorption of 100 nm polystyrene particles (4 mg/mL) was found to be up to 250-fold higher
compared to larger-sized (500 nm, 1 and 10 μm) polystyrene microparticles (4 mg/mL) (Desai et al.
1996).
Nevertheless, no data are available that link the GI absorption of polystyrene NPs to negative
effects in rats. In addition, the variety of NPs tested with different physicochemical properties, the
heterogeneity in experimental protocols, and the higher amount of M-cells in Peyer's patches of
rodents compared to humans shows the need for proper transport studies in humans (Des Rieux
et al. 2006). Unfortunately, clinical transport studies with NPs are currently still missing.
Earlier reports by Jani et al. indicated that orally administered NPs can be absorbed across the
GI tract via the lymph nodes to the liver and spleen (Jani et al. 1990). Reports by Yoshifumi showed
that NP substances are easily taken up by reticuloendothelial cells during drug transfer. The uptake
of these variably sized particles can lead to different toxicological effects (Yoshifumi 2002). Studies
on polystyrene latex NPs in the range of 50 nm-3 μm have shown that maximal absorption can
occur with particles sized approximately 50-100 nm in diameter (Hussain et al. 2001). On the other
hand, further studies by Hussain et al. found that even latex particles above 1 mm can be retained in
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