Biomedical Engineering Reference
In-Depth Information
A very recent study by Sun et al. suggested that the intratracheal instillation of TiO
2
NPs for
90 consecutive days leads to its successive accumulation in mouse lungs. Thereafter, the accumu-
lated TiO
2
NPs can significantly increase lung indices and induce histopathological changes in the
lung (including emphysema, edema, inflammatory cell infiltration, congestion of blood vessels, and
pulmonary bleeding [107]). Adult male ICR mice exposed to a single intratracheal dose of TiO
2
NPs showed emphysema, macrophage accumulation, extensive disruption of alveolar septa, type
II pneumocyte hyperplasia, and epithelial cell apoptosis in the lung [108]. Warheit et al. demon-
strated that exposure to intratracheal instillations of TiO
2
NPs produced pulmonary inflammatory
responses in the rat lung [109,110]. Chen et al. observed alveolar septal thickening, neutrophil infil-
tration, and thrombosis in the pulmonary vascular system in mice after an intraperitoneal injection
of TiO
2
NPs (3.6 nm) for 7 days [111].
Several studies have addressed the pulmonary effects induced by TiO
2
during inhalation experi-
ments in rats [112,113]. A few studies have also investigated how agglomeration influences the
relationship between the NP exposure dose and the induction of pulmonary toxicity [105]. However,
the initial size of the agglomerates is a factor that determines their deposition in the lung, their
ability to cross biological barriers, and their capacity to reach and enter cellular targets [45,114].
For instance, bigger NP agglomerates (>100 nm) are more likely to promote pulmonary clearance
by alveolar macrophages than smaller agglomerates, thus reducing persistence time in the airway.
Alternatively, small NP agglomerates (<100 nm) may escape the pulmonary defense systems and
induce deleterious effects by interacting with lung cells [105].
After administration, NPs may translocate to blood circulation and become entrapped in other
tissues/organs [115,116]. Berry et al. first confirmed the translocation of 30 nm particles across
the alveolar epithelium into pulmonary capillaries by intratracheal instillation. There was a rapid
translocation (~30%) of instilled 99mTc-labeled NPs in 5 min from the lung to the bloodstream in
hamsters [117,118]. Both
in vivo
and
in vitro
studies have shown that some NPs (including TiO
2
),
can cause injurious effects on biological systems, whereas larger particles of the same substance are
relatively less toxic [119,120]. Differences in toxicity have been attributed to the small size of the
NP, their large surface area or high surface reactivity, their crystal phases, and their prolonged resi-
dence times in the lung [110]. The measurement of the surface area of NPs has been widely studied
and has shown the potential for relating NP exposure dose and pulmonary responses [64]. Hence, it
can be stated that the continued use of TiO
2
NPs as a biomaterial requires its biological impact and
toxicity to be assessed accurately and alleviated where possible.
11.4.4 a
lBuMIN
The name albumin derives from the early German term “albumen,” generally indicating proteins.
Albumen, on the other hand, derives from the Latin word, albus (white), indicating the white part of
the cooked egg surrounding the yolk. It is basically a polymer that consists of a single polypeptide
chain and exists mainly in the α-helical form [121,122]. Albumin can be found in egg whites and
in blood. The three-dimensional structure of human serum albumin (HAS) has been determined
by x-ray crystallography to a resolution of 2.5 Å. It is composed of three homologous domains that
gather to form a heart-shaped molecule [123,124]. Each domain is a product of two subdomains that
bears a universal structural design. The primary binding regions for ligands to HSA are located in
hydrophobic cavities in subdomains IIA and IIIA, which exhibit similar chemistry. Structurally,
the serum albumins are similar, with each domain containing 5-6 internal disulfide bonds [124].
Albumin has numerous unique properties that make it an attractive drug vehicle in medicine. It is a
versatile carrier for an array of hydrophobic drugs and biomolecules, including hormones, vaccines,
DNA, siRNA, and vitamins [125-127].
NPs made of HSA offer numerous advantages, including ease of preparation, reproducibility,
and propensity to undergo surface modifications (ligand binding), as well as its high tolerability and
biodegradability in a given bioenvironment [128-130]. Impending drug molecules can be integrated
