Biomedical Engineering Reference
In-Depth Information
nanomaterials may sometimes enter the bloodstream and translocate to other organs. It remains
unclear, due to limited data, how extensive these potential adverse effects may be, and the literature
suggests that adequate precautions must be exercised when it comes to the application of nanomate-
rials. Therefore, the role of engineered nanomaterials in therapeutic settings needs to be completely
understood before their full potential can be realized.
The respiratory system symbolizes a distinctive target for the possible toxicity of NPs due to the
fact that, in addition to being the port of entry for inhaled particles, it also receives the entire cardiac
output. As such, there is a potential for exposure to the lungs for NPs that are introduced to the body
via vivid exposure routes (like dermal, gastrointestinal, injection, etc.) that may result in its systemic
distribution [44,45]. The principle machinery responsible for the deposition of inhaled nanosized
particles in the respiratory tract is diffusion. Additionally, numerous defense mechanisms exist
throughout the respiratory tract aimed at keeping the mucosal surfaces free of cell debris and par-
ticles deposited by inhalation. Once deposited, nanosized particles translocate readily to extrapul-
monary locations and reach other target organs by various transfer routes and mechanisms. Once
the particles arrive at pulmonary interstitial sites, their uptake into blood circulation (in addition to
lymphatic pathways) can also occur.
Nanomaterials can gain access to the bloodstream following inhalation and ingestion, where-
upon they can be taken up by organs and tissues, including the brain, heart, liver, kidneys, spleen,
bone marrow, and nervous system [46,47]. Hence, in addition to lung effects, within the last few
decades, considerations of particle toxicology have also encompassed possible systemic effects
[48,49]. An interest in the respiratory system as a target for the potential effects, both beneficial and
adverse, of NPs is reflected by the steady increase in the number of scientific publications on these
subjects during the past few decades. The studies have shown that, in the case of lung diseases, the
buildup of even harmless matter may harm its function and enhance its damage. CNTs were found
to be more toxic, and recent studies have shown it to cause the death of kidney cells and to inhibit
cell growth by decreasing cellular adhesion [50,51]. Recently, researchers throughout the globe are
exploring toxicity issues associated with various nanomaterials that are proficient in carrying, as
well as delivering, loaded bioactives (drug, gene, diagnostic agents, etc.) to sites of action.
The purpose of this chapter is to complement and expand on the understanding of the pulmonary
effects of various nanomaterials by providing an overview of potential applications as well as asso-
ciated toxicity concerns, with a special emphasis on drug and gene delivery.
11.4.1 c arBoN N aNotuBes
CNTs are essentially cylindrical molecules composed exclusively of carbon atoms [52]. They basi-
cally exist in two distinct classes, namely, single-walled carbon nanotubes (SWCNTs) and multi-
walled carbon nanotubes (MWCNTs). SWCNTs are long, wrapped, graphene sheets that are mostly
considered one-dimensional [53], while MWCNTs are larger structures that are composed of sev-
eral SWCNTs arranged one inside the other (Figure 11.4). CNTs could be one of the most promis-
ing nanovectors for the proficient delivery of drugs and biomolecules due to their huge surface
area and exceptional properties. They can be conjugated noncovalently or covalently with drugs or
biomolecules toward the development of a new-generation delivery system. CNTs bear the capac-
ity to interact with mammalian cells and enter cells via cytoplasmic translocation; hence, they can
deliver a range of therapeutic reagents into the cell. For example, plasmid DNA contained within
the CNT may be internalized by the cell, and the expression of the plasmid-carried marker genes
has been shown to be enhanced [54-56]. The unique and diverse properties of CNTs, including their
capability to undergo chemical modification for a variety of applications, make them an excellent
and widely explored nanomaterial. They are of a nanometeric size and bear the immense capacity
to interact with macromolecules such as drugs, proteins, peptides, DNA, RNA, and siRNA [57-59].
In addition to the wide range of literature describing the biomedical application of CNTs, reports
are also available on toxicity issues associated with this application. The toxicity of CNTs is closely
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