Biomedical Engineering Reference
In-Depth Information
physiologically based pharmacokinetic models for two complementary
functions: (i) to extrapolate
in vivo
results obtained for a given nanoparticle
to particles of the same kind but of different sizes or with different surfaces
and (ii) to relate the biological concentration and internal doses tested in
in vitro
experiments and in high-throughput screening toxicity testing to
external doses in terms of intake or uptake. Thus far, physiologically based
toxicokinetic (PBTK) models have typically been developed for specific indi-
vidual chemicals, with little attempt to generalize to key physico-chemical
properties associated with nanoparticles. However, toxicokinetic data and
models are beginning to emerge for nanoparticles, reflecting mechanisms
at different scales: Wilhelm et al.
188
and Luciani et al.
189
present a model of
endocytosis of negatively charged iron oxide superparamagnetic nanoparti-
cles described as a two-step process: a Langmuir adsorption for the binding
of anionic magnetic nanoparticles onto the cell surface followed by a satu-
rable cell internalization mechanism. Semmler et al.
190
provide experimen-
tal clearance kinetics of inhaled ultrafine insoluble iridium particles from
the rat lung, including transient translocation into secondary organs. Lin et
al.
152
provide a first PBTK for quantum dots based on experimentally derived
blood-to-tissue distribution ratios. Wenger et al.
191
have shown that the resi-
dence time and biodistribution of nanopolymers in the body was directly
related to particle size (Figure 11.12).
Since accumulation of nanoparticles in tissues and especially in the liver
appears to be linked to macrophage uptake, Li et al.
190
has developed and
100
10
Wenger (2011) PAA
Wenger (2011) PAA-PEG
Ya ng (2009) Nanogel PEG
Ya ng (2009) Nanolatex PEG
Panagi (2001) PLGA
Panagi (2001) PLGA-mPEG
Gratton (2007) PRINT-PEG
Gaucher (2009) PLA-PVP
Gaucher (2009) PLA-PEG
Lui (2008) Coated BVP-PLA
1
0.1
0.01
0.001
350
50
100
Nanoparticle size (nm)
150
200
250
300
0
FIGURE 11.12
Comparison of maximum half-lives in blood with results of five other experiments on
pegylated (empty symbols) and nonpegylated (filled symbols) polymeric nanoparticles. (From
Wenger, Y. et al.,
Toxicol. Appl. Pharmacol.
,
251,
181, 2011.)
