Biomedical Engineering Reference
In-Depth Information
It behooves pharmaceutical researchers to develop nanotechnologies that bypass these invasive
methods. Such particles improve tissue penetration, bypassing IVT, and provide sustained drug or
gene therapy, a possible advantage that would bypass the need for viral gene therapy. However, this
method is not without its own risk of infection and hemorrhagic complications [2,4,5]. By being
able to control the dramatic increase in surface-area-to-volume ratio of nanoparticles as compared
to comparable macroscopic devices, researchers could enhance tissue penetration and drug-delivery
systems directly to the affected tissue [4,6].
The accessibility of the eye makes it a great target for nanoparticle therapy [2]. However, such
technologies are not without their own drawbacks. Nanoparticles may be coated with toxic chemi-
cals that could be released into the body during therapies or may build up into tissues and cause
blockages, leading to an increase in interocular pressure [3,4]. The retina and optic neural tissue are
very sensitive to toxic materials, which may cause unforeseen complications due to seepage of toxic
materials during therapy [2,5,6].
The most common forms of nanoparticle toxicity that are expressed in the ocular tissue are
oxidative stress, counteractions with cell membranes, and inflammation [2]. These parameters
were tested in the trials conducted with the following nanoparticles outlined in this section of
the chapter. Since the rabbit is the most common animal model used for ocular toxicity studies,
most of the studies cited used this animal to obtain toxicity data [2]. The large lens of the mouse
and rat makes them poor models, as administrating intraocular injections proves difficult [2]. In
addition, a number of ocular complications arise in the mouse or rat by even the slightest touch
of the eye by the needle, including inflammation or the development of cataracts [2]. Monkeys'
eyes provide the best model for studying ocular toxicity of nanoparticles, but none of the fol-
lowing studies cited used the monkey as a model for the respective toxicity studies; it is unsure
why not [2].
16.1.1 N
aNocerIa
One of the causes of retinal degenerative diseases, such as diabetic retinopathy, is oxidative damage
due to reactive oxygen radical species [6]. Cerium oxide nanoparticles, also known as nanoceria,
have been developed as antioxidants and free radical scavengers as a potential therapy for such
neurodegenerative diseases [6]. When these nanoparticles are synthesized in the 3-5 nm range, they
mimic the effects of the antioxidant enzymes, such as superoxide dismutase and catalase, which
neutralize superoxide anions and hydrogen peroxides, respectively [6-8].
The primary method of administration for the nanoceria particles was via IVT. After injection,
the retinal tissue accumulated the greatest concentration of nanoparticles and 70% of the particles
were retained 120 days postinjection [6]. Nanoceria was not actively eliminated from the eye, as
90% of the injected nanoceria was retained in the eye 120 days postinjection [6]. The experimental
half-life yield of the nanoceria in the retina was 414 days with a half-life of 525 days in the eye.
Studies by Asati et al. [9] showed that the polymer coating of the nanoceria particles may induce
a charge on the particles, varying the rates of uptake in different tissues and inducing localization
in certain tissues. They also found that positively charged nanoceria particles could be taken up by
more cell types than negatively charged particles [9].
Previous studies showed that weekly injected nanoceria did not have cytotoxic effects in the
heart, kidney, brain, lung, spleen, and liver; cytotoxic studies in the ocular tissue also showed that
nanoceria did not have toxic effects on healthy retinal tissue over a range of doses [6]. Investigations
of four types of retinal tissue—superior and inferior central retina and superior and inferior periph-
eral retina—9 days post-IVT injection showed that there was no reduction in the thickness of these
layers. This finding along with the lack of observable change in retinal function postnanoceria IVT
injection as compared to saline-injected eyes further suggests that nanoceria does not have any short-
or long-term cytotoxic effects on retinal tissue [6]. In addition, nanoceria particles were shown to be
nontoxic to the optical neural tissue up to 120 days postinjection [6].
