Biomedical Engineering Reference
In-Depth Information
from animal toxicological studies. These factors, including size, surface area,
surface chemistry, solubility, and shape, will influence both the deposition
of NPs in the lungs and the biological responses observed. Maynard and
Kuempel [17] reported that NPs, including carbon black (12 nm), elemen-
tal carbon (90 nm), and diesel exhaust particulate (120 nm), caused various
cytoskeletal dysfunctions. These dysfunctions included impaired phagocy-
tosis, inhibition of cell proliferation, and decreased cell viability in primary
alveolar macrophages from dogs and mice from alveolar macrophage cell
lines in 24 h, depending on the dosages [17]. Monteiro-Riviere and colleagues
[19] reported an important observation, saying that if the carbon nanotubes
reach the lung tissue, then they were more toxic than similarly chemically
composed NPs, such as carbon black or quartz dust (actually these two NPs
are known for their lung toxicities). Monteiro-Riviere and colleagues [19]
argued that the observation was due to the tendency of carbon nanotubes
to self-aggregate and then remove themselves from the controlled condition.
These agglomerated NPs have a much higher residence time than dispersed
NPs.
NPs that leave the lungs might enter the blood circulation, and then may
cause endothelial cell injury (of the blood vessels) and prothrombotic effects
[20]. Recent studies have indicated that NPs depositing in the nasal region
may be transported to the olfactory bulb via the olfactory nerves [21]. The
same group exposed rat to manganese ultrafine particles <100 nm during 12
days and observed an accumulation in the olfactive bulb. The authors con-
cluded that the olfactory neuronal pathway is efficient for translocation. They
also mentioned a nonprimate study in which the authors noted a similar
observation, suggesting the plausibility of the olfactive pathway for humans
[22]. The size of NPs may also penetrate cells and cellular organelles. In a
study of concentrated NPs from air pollution in human bronchial epithe-
lial cells and mouse alveolar macrophages, the ultrafine fraction (<100 nm)
was found to penetrate into cells and localize in mitochondria, causing oxi-
dative damage to mitochondrial membranes [23]. Unlike low molecular
weight drugs, which penetrate cells easily, the cellular uptake of polymeric
prodrugs is restricted to the endocytic route, which basically means that
prodrugs are delivered to the cellular lysosomes [3]. However, other stud-
ies of drug delivery across the blood-brain barrier further confirmed the
importance of surface properties, showing that particle surface components
may bind to the apolipoprotein E receptor, which mediates crossing of this
highly complicated tight barrier [3]. The olfactory neuronal pathway rep-
resents a significant exposure route of central nervous system (CNS) tissue
to inhaled solid manganese oxide NPs. In rats, which are obligatory nose
breathers, translocation of inhaled NPs along neurons seems to be a more
efficient pathway to the CNS, than via the blood circulation across the blood-
brain barrier for humans. Given that this neuronal translocation pathway
was also demonstrated in nonhuman primates, it is likely to be operative in
humans as well [24].
