Biomedical Engineering Reference
In-Depth Information
TABLE 7.4
Applications, Concerns, and Biological/Mechanistic Studies of Inhaled Nanoparticles of
Particle Size Less than 100 nm and Greater than 500 nm
Nanoparticles (
<
100 nm)
Larger Particles (
>
500 nm)
General Characteristics
Ratio: Particle number/mass or surface
area/mass
High
Low
Agglomeration/aggregation in air and/or
liquids
Likely (depends on medium)
Less likely
Deposition in respiratory tract protein/
lipid adsorption in vitro
Diffusion dominates
Yes, important for biokinetics
Sedimentation, impaction, and
interception dominate
Translocation to Secondary Target Organs
Clearance
Ye s
Less important
Mucociliary
Probably yes
Generally not
Alveolar macrophages
Poor
Efficient
Epithelial cells
Ye s
Efficient
Lymphatic circulation
Ye s
Mainly under overload
Blood circulation
Ye s
Under overload
Sensory neurons (uptake and transport)
Ye s
Under overload
Protein/lipid adsorption in vivo
Ye s
No
Cell entry/uptake
Yes (caveolae, clathrin, lipid rafts,
diffusion)
Some
Primarily phagocytic cells
Mitochondria
Ye s
No
Nucleus
Yes (<40 nm)
No
Direct Effects (Chemistry and Dose Dependent)
At secondary target organs
Ye s
No
At portal of entry (respiratory tract)
Ye s
Ye s
Inflammation
Ye s
Ye s
Oxidative stress
Ye s
Ye s
Activation of signaling pathways
Ye s
Ye s
Primary genotoxicity
Some
No
Carcinogenicity
Ye s
Ye s
Source:
Adapted from G. Oberdörster,
Journal of Internal Medicine
, 267, 2010, 89-105. With permission.
nanometer-scale particles, a significantly greater inflammatory response in the lungs occurs in com-
parison to the exposure to the larger particles with an identical chemical composition (TiO
2
and
Al
2
O
3
) [64-66]. The results were based on the same mass ratio. It was concluded that this greater
inflammatory response was due to an increased rate of interstitialization of 20-30 nm nanometer-
scale particles compared with 200-500 nm in the lungs. Another study by Oberdürster et al. [67]
also showed that inflammatory responses following inhalation in rats depended on particle size;
however, when normalized by surface area, size-invariant dose-response function was observed.
Some reports of PN toxicity has been reported recently. In this study, the influence of the size
of poly (lactic-
co
-glycolic acid) (PLGA) and titanium dioxide (TiO
2
) nanoparticles on cytotoxicity
was determined. Nanoparticles of three different sizes were studied in two cell lines—RAW264.7
cells and BEAS-2B. Size-dependent cytotoxic effects were observed after incubation with PLGA
or TiO
2
nanoparticles for 24 h. Even though PLGA nanoparticles did not activate significantly fatal
toxicity, it was found that it led to tumor necrosis factor alpha (TNF-a) release. It was also observed
