Biomedical Engineering Reference
In-Depth Information
Main factors affecting absorption in
oral cavity
1. Formulation related
2. Surface area available for
absorption/particle size
3. Oral cavity physical/pathological
condition
Toxic
effects
can be
observed
Absorption in oral cavity
Blood: extensive binding to albumin
and lipoproteins
Toxic
effects can
be
observed
Wide and
extensive
distribution
Accumulation
in fat
Distribution
Liver
Toxic
effects can
be
observed
Biotransformation
Fat
Excretion
Bile
Urine < 2%
Feces > 90%
FIGURE 24.1
Schematic description of toxicokinetics for oral nanoparticulate drug delivery systems.
24.3.2
Acute and chronic toxicity
Nanoparticles because of their small size and increased surface area give them a different toxic-
ity profile than their bulk chemical or larger particles of the same chemical composition
[45]
.
An example of acute toxicity with nanoparticles is with nickel. A 38-year-old healthy man was
exposed to nanoparticle-sized nickel while spraying them onto bushes for turbine bearings using
a metal welding technique
[46]
. The patient died 13 days later. The inhaled nickel nanoparticle
caused adult respiratory distress syndrome as well as acute tubular necrosis in the patient.
Transmission electron microscope observation showed that nickel nanoparticles of
25 nm
were present in lung macrophages of the patient. Nickel is a well-known toxicant and therefore,
it is unlikely to be used as a dental nanoparticle drug delivery system. However, this occupa-
tional exposure provides clinically important insights into the acute toxicity of nanoparticles in
humans. A small number of nude mice were intravenously given functionalized SWCNTs over
a 4-month-period and the mice did not show signs of acute or chronic toxicity
[47]
.However,
the functionalized SWCNTs persisted in liver and spleen macrophages of the mice over the
4 months which could be a concerning observation to be followed up in future larger animal
studies.
,
