Biomedical Engineering Reference
In-Depth Information
1.6.3.3 Reticuloendothelial Systems
Since all of the blood exiting the GIT goes into the hepatic portal vein that directly diffuses through
the liver, the RES system in the liver is exposed to all NPs absorbed from the GIT into the car-
diovascular system (CVS). NPs such as carbon black and polystyrene exert their toxic effects by
enhancing the secretion of proinflammatory cytokines, such as tumor necrosis factor alpha, fol-
lowing the stimulation of macrophages via ROS and calcium signaling (Brown et al. 2004). These
proinflammatory cytokines and oxidative stresses that can potentially damage hepatocyte function
and bile formation are also associated with the pathology of liver diseases (Wani et al. 2011). The
direct injection of ultrafine carbon black particles into the blood induces platelet accumulation in the
hepatic microvasculature of healthy mice in addition to prothrombotic changes on the endothelial
surface of hepatic microvessels.
1.6.3.4 Cardiovascular System
The surface charge of NPs plays a vital role in their toxic effects on the CVS. Especially cationic,
ultrafine particles, such as gold and polystyrene, have been shown to cause a lethal effect on RBCs
and blood clotting while anionic particles are found to be nontoxic. The exposure to diesel exhaust
particles (DEPs) was found to alter heart rates in hypertensive rats, while also inducing direct, nega-
tive effects on the heart's pacemaker activity (Hansen et al. 2007). Exposure to SWCNT has also
resulted in adverse cardiovascular effects (Li et al. 2007).
1.6.3.5 Central Nervous System
The brain can be exposed to NPs by the means of two different mechanisms after inhalation;
namely, trans-synaptic transport after inhalation through the olfactory epithelium and uptake
through the blood-brain barrier (Jallouli et al. 2007, Lockman et al. 2004). The adverse patholo-
gies, including hypertension and allergic encephalomyelitis, have been found to be associated with
the enhanced permeation of NPs to the blood-brain barrier in experimental setups. The production
of ROS (Long et al. 2006) and subsequent oxidative stress (Peters et al. 2006) by NPs has been
implicated in the pathogenesis of neurodegenerative diseases, such as Parkinson's and Alzheimer's.
The NP's surface charges and chemical compositions have been shown to alter blood-brain integ-
rity and deserve considerations as to their role in brain toxicity and distribution (Wani et al. 2011).
1.6.3.6 Integumentary System
The skin is the largest primary defense organ in our body and comes into direct and indirect con-
tact with many toxic agents. The strongly keratinized stratum conium is the rate-limiting barrier to
defending against the penetration of most micron-sized particles and harmful exogenetic toxicants.
Possible skin exposure to NMs can also occur during the intentional application of cosmetics and
other topical drug treatments. In addition, NPs have unique scattering properties due to their small
size. They may alter the optical pathway of UV photons entering the upper part of the skin's horny
layer. In this way, more photons can be absorbed by the stratum conium.
In vitro
studies have shown
that MWCNT initiate an irritation response in human epidermal keratinocytes by their localizing
effect (Baroli et al. 2007, Zvyagin et al. 2008). QDs with diverse physicochemical properties were
found to penetrate the intact stratum conium barrier and get localized within the epidermal and
dermal layers (Ryman-Rasmussen et al. 2006).
1.7 NANOTOXICITY: CHALLENGES, SOLUTIONS, AND THE FUTURE
Unfortunately confined just to nanomedicine, toxicity assessments are an integral part of NM devel-
opment. Even though attempts are being made to assess toxicity of widely used NMs, they are
met with various challenges owing to the shortcomings of the methods used for assessment. Even
though nanotoxicology is considered a well-defined field, it faces a lot of challenges even today.
