Biomedical Engineering Reference
In-Depth Information
adduct formation by the production of elevated free radical levels in lung tissue [178]. However, TiO 2
nanoparticles were not able to induce DNA breakage, as displayed by ferric oxide nanoparticles
[175,178]. DNA damage was shown to be dose dependent in silver nanoparticle activity [179]. TEM
images indicating the presence of silver nanoparticles in cellular nuclei and mitochondria implicate
these nanoparticles in the production of ROS, leading to mitochondrial toxicity and DNA damage
[179]. Cells exposed to silver nanoparticles spent more time in the G 2 /M cell cycle phase to repair
the damage done to DNA [179].
9.3.4 h ealth e ffects of o rgaNIc N aNopartIcles
An advantage of the use of organic nanoparticles as opposed to inorganic nanoparticles is the pos-
sibility of reduced cytotoxicity due to oxidative stress seen in inorganic nanoparticles. A number of
organic nanoparticles have been developed and used, and have been relatively successful in reduc-
ing cytotoxic effects in cells. However, the chemicals used in the preparation of organic nanopar-
ticles have the ability to induce cytotoxic effects in in vitro models.
Solid lipid nanoparticles (SLNs) are made of biocompatible lipids and waxes with various sizes
and alkyl polymer length, depending on the preparation method employed [180]. However, owing
to the hydrophobic surface properties of these nanoparticles, they are prone to becoming complexed
with plasma proteins and cytokines, facilitating their clearance from the blood stream by phagocytic
cells [180]. However, the use of surfactants in the synthesis of these polymers in efforts to modify the
surface properties of SLN could potentially affect phagocytic activity, thereby enhancing the particle's
therapeutic efficiency in biological settings [180]. The use of surfactants previously shown to be rela-
tively safe would reduce any cytotoxic potential in the nanoparticles. However, the size of the SLN and
alkyl chain length may also contribute to its cytotoxicity: longer chain lengths and smaller particles
tend to be more toxic [180]. Moreover, a similar surfactant-induced cytotoxicity effect is displayed
by certain surfactants used in the production of edible lipid nanoparticles—used in the food industry,
and PLGA nanoparticles (polymers of polylactic acid and polyglycolic acid) [181,182]. In the case of
the PLGA nanoparticles, the modified surface charges of the nanoparticles were also able to induce
inflammatory responses in addition to the responses induced by the surfactants, as measured by the
release of cytokines and interleukins [181]. Related to the cytotoxic effects of functional groups in
SLNs, a similar phenomenon was displayed in acylated starch nanoparticles, which induced higher
cytotoxicity via aromatic group substitution as compared with aliphatic group substitution [183].
Chitosan, a biopolymer produced by the deacetylation of chitin obtained from crustacean
shells, is widely used in the production of nanoparticles [184,185]. Owing to its poor solubility at
physiological pH, the modification of chitosan with oligosaccharides enables its solubility in water
and several organic solvents, enabling effective drug delivery in low cytotoxic levels [184,186].
Unmodified chitosan displays an almost-zero zeta potential, imparting bio-inert qualities that would
reduce irritation to surrounding tissue [185]. It shows great biocompatibility, very low cytotoxicity,
and biodegradability [185]. In addition, its cationic surface charge allows it to complex with DNA,
imparting stability and functioning as a possible transfection agent following surface modifica-
tion [185]. However, because chitosan is a carbohydrate-based compound derived from crustacean
shells, it has the possibility of inducing an immune response in the presence of antigens to surface
modifications [187]. However, these would vary by individual and targeted tissue.
Nanomicelles, self-assembling nanoparticles with a hydrophobic core and hydrophilic shell, are
an emerging therapeutic vector [188]. Many hydrophobic drugs are blocked from uptake by tissue
because of the hydrophilic nature of the tissue; nanomicelles entrap the hydrophobic drug in its core
and the hydrophilic surface enables the particle to penetrate hydrophilic tissues [188]. Relatively
high levels of entrapment can be achieved by this method and the particles are stable in tissue for an
extended period of time, enhancing therapeutic effects [188]. Nanomicelles' small size and very low
toxicity provide for an emerging therapeutic model that should be considered in future in vitro and
in vivo testing to allow its large-scale therapeutic development [188].
Search WWH ::




Custom Search