Biomedical Engineering Reference
In-Depth Information
However, the major concern is that NPs could gain access to other organs, once having entered
the body and reached the bloodstream [26]. Biodistribution studies of NPs revealed the low con-
centrations in liver, spleen, heart, and the brain [39,40]. Further concerns are the bioaccumula-
tion of NPs in certain organs [41]. It is not yet clear to what extent the body is able to excrete NPs
via urine [42] or whether residual NPs bioaccumulate in certain organs and may block the body's
excretion systems. Certain types of NPs can pass through the gastrointestinal tract (GIT) and are
rapidly eliminated in feces and urine. These indicate that the absorption occurs through the GIT
barrier and entry into the systemic circulation [43]. However, some of the nanoparticulates can
accumulate in the liver during first-pass metabolism [5]. After intravenous administration, NPs
get distributed to the colon, lungs, bone marrow, liver, spleen, and the lymphatics [26,44,45].
Such distribution is followed by rapid clearance from the systemic circulation, predominantly by
action of the liver and spleenic macrophages [46]. Clearance and opsonization of NPs depends
on size and surface characteristics [43]. Differential opsonization translates into variations in
clearance rates and macrophage sequestration of NPs [46]. To increase the passive retention of
nanomaterials in systemic circulation, the suppression of opsonization events is necessary at
desired sites or anatomical compartments. For example, in the case of hydrophobic particles, a
coating with poly(ethylene) glycol (PEG), would increase their hydrophilicity, hence increasing
the systemic circulation time [47]. Whereas, PEGylated (polyethylene glycol coated) gold NPs
(size range 10-30 nm) did not cross the perfused human placenta and are not detected in fetal
circulation.
The inhaled NPs are distributed to the lungs, liver, heart, kidney, spleen, and brain [26,48,49].
The inhaled ultrafine silver NPs were distributed in the liver, lungs, and brain in rats. The NPs are
cleared from the organs via phagocytosis in the alveolar region by macrophages [47].
The distribution of gold NPs into different organs depends on the size of them. The gold NPs
having the size range <10 nm widely distributed in the blood, liver, spleen, kidney, testis, thymus,
heart, lung, and brain whereas the larger particles (50, 100, and 250 nm) were detected only in the
blood, liver, and spleen.
Owing to characteristic internalization and systemic distribution of inorganic and polymeric NPs,
there is a growing interest in exploring their uses for imaging, systemic delivery of drugs, target-
specific killing of cancerous cells, and so on. Understanding the relationship between the physico-
chemical properties (size, surface charge, hydrophilicity, etc.) of NPs and their ADME (absorption,
distribution, metabolism, and elimination) characteristics is critical to achieve the desired biological
effect. Muller et al. [88] have extensively reviewed the commonly studied nanomaterials, namely,
iron oxide NPs, dendrimers, mesoporous silica particles, gold NPs, and CNTs with reference to
their toxicity, biocompatibility, biodistribution, and biodegradation.
19.4 CONVENTIONAL RISK ASSESSMENT
The risk assessment is a very complex process. It involves the integration of information across a
range of domains including source characterization, fate and transport, modeling, exposure assess-
ment, and dose-response characteristics. It uses well-defined quantitative models to describe the
relationships between the various elements of the paradigm shown in Figure 19.3. Here, we have
briefly described how health risks have been traditionally identified and quantified based on infor-
mation about exposure and dose-response relationships. Implicit in this process is the setting of
“standards” or guidelines regarding “safe” or “acceptable” levels of exposure for a population.
Figure 19.3 shows the relationship between the general environmental health framework (in the
center) and the risk assessment framework.
Exposure is defined as the intensity of contact between the contaminant and the relevant biologi-
cal sites of impact over a relevant time period. Exposure assessment includes assessing sources of
pollutants and their strengths, measuring or modeling concentrations in environmental media, mea-
suring or modeling human exposures through various pathways, and in some cases, even biological
