Biomedical Engineering Reference
In-Depth Information
large particles did not cross (Szentkuri 1997). Nonbiodegradable latex particles can quickly perme-
ate the mucus when they are coated with PEG. Surprisingly, 200 nm particles crossed the mucin
layer faster than <100 nm nanomaterials (Wang et al. 2007a). These findings suggest that the surface
charge plays a crucial role in the transport rates of NPs through a mucus layer.
The lifetime of the mucus is short and the fastest turnover (i.e., clearance time) is observed at
surfaces with the thinnest mucus layers. Hence, NPs have to rapidly permeate through this barrier
to reach the underlying epithelia (Cone 2009). Local effects after oral exposure to nanomaterials
include abnormal mucus production, induced by TiO
2
NPs in cultured ChaGo-K1 cells (Chen et al.
2011) and by silver NPs
in vivo
(Jeong et al. 2010). In addition, pH changes induced by nanomaterials
can change the pH-dependent aggregation of mucins (Bhaskar et al. 1991). Additionally, positively
charged nanomaterials impede mucin swelling and thereby increase viscosity (Chen et al. 2010).
13.3.3 e
pIthelIal
l
ayers
of
the
o
rogastroINtestINal
t
ract
The epithelium generally represents the highest resistance against the passage of chemical com-
pounds and nanomaterials. Epithelial cells are polarized; they have an apical surface facing an
internal or external surface and a basal site, where they confront the underlying tissue. The epithelia
may consist of several layers and may vary in the height of the cells.
Penetration through a monostratified squamous epithelium, such as in the endothelia (Figure
13.2a), is easier than through the simple columnar epithelium in the stomach and intestine (Figure
13.2b) or the squamous epithelium layer of the oral cavity and esophagus (Figure 13.2c). The thick-
ness of the nonkeratinized squamous epithelium in the oral cavity ranges between 550 and 800 μm
(Collins and Dawes 1987; Harris and Robinson 1992; Lagerlof and Dawes 1984). The squamous
epithelial layer of the esophagus shows a thickness of 300-500 μm (Takubo 2009). The epithelium
of the esophagus has the same structure as that of the buccal mucosa, but is thinner and less variable
(Diaz del Consuelo et al. 2005). The simple columnar epithelium found in the GI tract measures
20-25 μm (Atuma et al. 2001; Matsuo et al. 1997). Generally, only one cell type forms the structural
basis of the barrier: keratinocytes for the oral cavity and the esophagus, enterocytes for the small
and large intestine, and gastric epithelial cells for the stomach.
The epithelial cells are linked together by intercellular junctions, which provide mechanical
strength to the epithelial layer and restrict the passage between cells. In the oral mucosa, immune
cells (lymphocytes, Langerhans cells) are embedded in the keratinocytes layer (Figure 13.2d). The
epithelium of the stomach contains mucus neck cells that produce mucus; gastric chief cells that
produce pepsinogen and gastric acid; parietal cells that produce the intrinsic factor; and entero-
endocrine cells that produce a variety of hormones such as gastrin, serotonin, somatostatin, and
so on. (Figure 13.2e). Cells belonging to the immune system (M-cells), enteroendocrine cells, and
goblet cells are embedded in a layer of enterocytes in the small intestine region (Figure 13.2f).
M-cells are preferentially located in the epithelium overlying Peyer's patches, which is also known
as the follicle-associated epithelium (FAE), and delivers foreign substances to the underlying tissues
(mucosa lymphoid) to induce immune responses (Gerbert et al. 1996). However, M-cells are also a
potential portal for NPs. The large intestine epithelium consists of goblet cells and enterocytes. As
different cell types adjoin, the barrier property of the epithelium is altered because the location and
structure of these junctions differ between cell types (Eom and Choi 2009). All epithelia rest on a
basal membrane that separates them from the connective tissue lying underneath, which contains
capillaries, peripheral nerves, lymph follicles, and lymph vessels. To reach systemic circulation via
the capillaries, nanomaterials have to cross the basal membrane and connective tissue.
13.3.4 p
erMeatIoN
through
o
rogastroINtestINal
B
arrIers
I
n
V
Itro
The epithelia can be permeated either by passages through cells (transcellular) or by passages
between cells (paracellular). Physiological methods for evaluating interactions with biological
