Topics in Current Chemistry (2020) 378:8
1 3
intact human skin samples has been reported for several authors (with particle size
in a narrow range between 19 and 25 nm), suggesting that ion release is the most
feasible penetration mechanism [34, 35]. Whilst, for AuNPs, penetration through
intact human skin samples (size ~ 12 nm) has been demonstrated by several authors,
although the penetration process is unclear, although the ions release mechanism
could be discounted. The absence of Au ions in physiological solutions of AuNPs
has been reported, indicating higher long-term colloidal stability than AgNPs [30,
36]. This high stability could explain the absence or low cytotoxicity of this type of
plasmonic NPs.
2.2 Particle Size Effects
Although the literature reports contradictory results on this issue, skin penetration
of NPs is considered a size-dependent process [30]. Note that the stability of the NP
coating should be taken into account because it plays a key role in the interactions
between skin and both NP core (see section on Influence of the Capping-Ligand,
Including Surface-Chemistry and -Charge), and the NPs (i.e., steric stabilization)
by avoiding particle aggregation when they come into contact with the stratum corneum and constituent cells of the skin, mainly keratinocytes.
A representative study showing that AuNPs penetrate through intact skin samples in a size-dependent manner was reported by Sonavane et al. [37], who analyzed
the penetration of 15, 102 and 198 nm citrate-capped AuNPs, with spherical shapes
and surface negative charge, through rat-skin and rat-intestine using Franz diffusion
cells. The smallest AuNPs showed higher permeation than the larger particles. In
a similar study with rats, Raju and co-workers reported that 22 nm citrate-capped
AuNPs showed higher penetration than 105 and 186 nm particles across the thick
stratum corneum of the plantar rat skin [38].
A key aspect of the experimental design for assessing the skin penetration of
plasmonic NPs is the in vitro or in vivo model used to perform the analysis. Indeed,
the choice of a biologically relevant and realistic model for studying the biological effect of NPs is a comparatively unexplored field [39]. Although rat, mouse and
rabbits have been used extensively for these penetration studies, pig skin is probably the most similar animal model to the human skin [40]. Pig and human skin
are structurally very similar in thickness and dermal-epidermal thickness ratio. Hair
follicles and blood vessel patterns in the skin are also similar. In addition, the thickness of the human skin varies considerably as a function of the body region, gender
and age, among other factors. For this reason, the results obtained are quite different
depending on the in vivo model used, and even depending on the part of the human
body used. An interesting study on porcine skin using AgNPs was reported by Samberg and co-workers [22], who evaluated the in vitro and in vivo toxicity of eight
different commercial AgNPs supplied by nanoComposix (San Diego, CA), such as
unwashed/uncoated (diameter of 20, 50, and 80 nm), washed/uncoated (20, 50, and
80 nm), and carbon-coated AgNPs (25 and 35 nm). They observed that the toxicity of AgNPs in human embryonic kidney (HEKs) was influenced significantly by
residual contaminants in their supernatant, and that AgNPs themselves may not be
222
Reprinted from the journal
1 3
intact human skin samples has been reported for several authors (with particle size
in a narrow range between 19 and 25 nm), suggesting that ion release is the most
feasible penetration mechanism [34, 35]. Whilst, for AuNPs, penetration through
intact human skin samples (size ~ 12 nm) has been demonstrated by several authors,
although the penetration process is unclear, although the ions release mechanism
could be discounted. The absence of Au ions in physiological solutions of AuNPs
has been reported, indicating higher long-term colloidal stability than AgNPs [30,
36]. This high stability could explain the absence or low cytotoxicity of this type of
plasmonic NPs.
2.2 Particle Size Effects
Although the literature reports contradictory results on this issue, skin penetration
of NPs is considered a size-dependent process [30]. Note that the stability of the NP
coating should be taken into account because it plays a key role in the interactions
between skin and both NP core (see section on Influence of the Capping-Ligand,
Including Surface-Chemistry and -Charge), and the NPs (i.e., steric stabilization)
by avoiding particle aggregation when they come into contact with the stratum corneum and constituent cells of the skin, mainly keratinocytes.
A representative study showing that AuNPs penetrate through intact skin samples in a size-dependent manner was reported by Sonavane et al. [37], who analyzed
the penetration of 15, 102 and 198 nm citrate-capped AuNPs, with spherical shapes
and surface negative charge, through rat-skin and rat-intestine using Franz diffusion
cells. The smallest AuNPs showed higher permeation than the larger particles. In
a similar study with rats, Raju and co-workers reported that 22 nm citrate-capped
AuNPs showed higher penetration than 105 and 186 nm particles across the thick
stratum corneum of the plantar rat skin [38].
A key aspect of the experimental design for assessing the skin penetration of
plasmonic NPs is the in vitro or in vivo model used to perform the analysis. Indeed,
the choice of a biologically relevant and realistic model for studying the biological effect of NPs is a comparatively unexplored field [39]. Although rat, mouse and
rabbits have been used extensively for these penetration studies, pig skin is probably the most similar animal model to the human skin [40]. Pig and human skin
are structurally very similar in thickness and dermal-epidermal thickness ratio. Hair
follicles and blood vessel patterns in the skin are also similar. In addition, the thickness of the human skin varies considerably as a function of the body region, gender
and age, among other factors. For this reason, the results obtained are quite different
depending on the in vivo model used, and even depending on the part of the human
body used. An interesting study on porcine skin using AgNPs was reported by Samberg and co-workers [22], who evaluated the in vitro and in vivo toxicity of eight
different commercial AgNPs supplied by nanoComposix (San Diego, CA), such as
unwashed/uncoated (diameter of 20, 50, and 80 nm), washed/uncoated (20, 50, and
80 nm), and carbon-coated AgNPs (25 and 35 nm). They observed that the toxicity of AgNPs in human embryonic kidney (HEKs) was influenced significantly by
residual contaminants in their supernatant, and that AgNPs themselves may not be
222
Reprinted from the journal