Biomedical Engineering Reference
In-Depth Information
the distribution of nanomaterials is more than likely to remain localized, a possible distribution
in the rest of the body may occur if the nanomaterial reaches deeper layers of skin in sufficient
concentrations.
Exposure to nanomaterials via the dermal route most commonly arises from topical applica-
tions as, more recently, nanotechnology is consistently being incorporated into wound dressings,
textiles, cosmetic products, and sunblock, among others [42,54,55]. Occupational exposure to
nanomaterials also presents a concern, as repeated exposure may alter the integrity of the integu-
mentary barrier and increase the permeation of nanomaterials. For example, a study by Rouse
et al. [61] demonstrated skin penetration of fullerene-based peptides
in vitro
using a porcine skin
model subjected to repeated mechanic stress. On the other hand, an exhaustive study by Baroli
et al. [62] demonstrated that metallic nanoparticles passively penetrate the hair follicle and
stra-
tum corneum
; however, the nanoparticles were unable to penetrate the full thickness of the skin
and remained in the dermis. The majority of the current literature reports limited to none skin
penetration by metallic nanoparticles often used in topical crèmes [63,64]. Smaller-sized nanopar-
ticles (less than 10 nm) are favored in permeation to the dermis layer, but nanoparticles as large
as 200 nm have been shown in the dermis layer via the penetration of hair follicles [64]. However,
limited studies are available on the role of specific nanoparticle parameters on skin permeation,
and the further building of the basis of understanding the mechanisms of permeation is necessary.
Overall, dermal delivery presents an exciting area of drug delivery research, where potential thera-
peutic applications of local drug delivery would have very limited toxic effects; however, further
studies are warranted to understand the mechanisms of nanoparticle translocation and metabolism
in all of the components of the skin.
9.2.2 r
ole
of
s
pecIfIc
N
aNopartIcle
c
haracterIstIcs
IN
d
eterMININg
h
ealth
e
ffects
The size of the nanoparticle yields a whole assortment of unique characteristics. With a decrease
in the average size of the particles, the surface-area-to-mass ratio drastically increases in parti-
cles sized 100 nm and below in diameter (Figure 9.3). Because of the large specific surface area,
nanoparticles tend to be highly reactive due to a high number of interaction points that could par-
ticipate in biochemical interactions. Thus, when considering the concentration of nanoparticles, the
number of particles and their size (i.e., surface area) provides more insight into the expected scope
of interactions.
The makeup and morphology of nanoparticles is another aspect that determines its physiochemi-
cal properties and the nature of its interaction with the environment. For instance, the shape of
nanoparticles plays a role in its uptake, such that rods experience the highest uptake by the cells,
followed by spheres, cylinders, and then cubes in nanoparticles sized larger than 100 nm [65]. This
phenomenon can be due to the number of interactions with the membrane, as rods have more inter-
actions with the membrane and are thus more likely to be taken up by the cell. However, at the
same time, nanoparticle spheres less than 100 nm in size are taken up better than rods due to the
fact that nanorods have two different orientations of interaction [66-68]. More interactions with
the membrane would facilitate phagocytosis; however, a vertical axis of interaction may be highly
unfavorable for uptake. Thus, nanorods require another level of specification: the placement and
orientation of their ligands [69,70].
Similar to the shape of the nanoparticle, the size also plays a role in determining the interactions
with the cell membrane. The smaller the nanoparticle, the larger the ratio of specific surface area to
size, making uptake more likely. However, normally a cell has a limited number of specific recep-
tors; if the nanoparticle size is too small and the concentration too high, localized overloading may
occur, such that the uptake may not be as efficient. Mathematical models dictate that the optimal
size occurs when there is no shortage of the ligand on the nanoparticle, with no localized shortage of
the receptor on the cell membrane [71]. The best size for cell uptake of spherical gold, silica, single-
walled carbon nanoparticles, and quantum dots has been experimentally determined to be 50 nm
