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Topics in Current Chemistry (2020) 378:8
deposition of AuNPs increased 2-fold after PEG-OAm functionalization, demonstrating a preferential accumulation mediated by the stabilizing ligand. Mahmoud
et  al. [65] evaluated the preferential accumulation of Au-nanorods into abdominal
human skin hair follicles. To this end, they prepared 11.4 × 46.6  nm Au-nanorods
with five different surface chemistries (i.e., neutral, anionic, cationic, and hydrophobic), such as CTAB, PAA, methoxy-polyethylene glycol-thiol (m-PEG-SH),
PEG-Cystamine, and polystyrene (PS). They observed that the lipophilic properties of sebum-rich hair follicles enhanced the accumulation of hydrophobic PS-Aunanorods into hair follicles, while neutral m-PEG-S-Au-nanorods were distributed
into all skin compartments, especially the dermis, which exhibits hydrophilic characteristics. In addition, both charged Au-nanorods showed a negligible percentage of
penetration into any of the skin compartments.
3 Bioconjugated Plasmonic NPs for Transdermal Delivery
of Different Cargoes
A seminal study on the development of bioconjugated plasmonic NPs for enhancing the skin penetration of different cargoes was reported in 2010 by Huang et al.
[56]. They demonstrated significant enhancement of the transdermal delivery of
protein-drugs by co-administration with 5  nm PVP-capped AuNPs. This fact was
attributed to the nano-bio interaction with skin lipids, which allowed a reversible
openings of the stratum corneum. Thus, this work provided a simple and efficient
NP-mediated method for overcoming the skin barrier for percutaneous protein drug
delivery. Labala et al. [66] reported the first bioconjugated plasmonic NPs for iontophoretic transdermal delivery of imatinib mesylate to treat melanoma, using an LbL
assembly approach. This LbL polymer capped AuNP contained PVP and polyethylene imine (PEI), was subsequentially coated with anionic poly(styrenesulfonate)
(PSS) and cationic PEI for drug loading. The resulting bioconjugated nanosystem
showed an average particle size and a zeta-potential of 98 ± 4 nm and + 32 ± 1 mV,
respectively, and a shift in the SPR wavelength from 518 to 530  nm. The in  vitro
skin penetration studies were performed on excised porcine ear, and demonstrated
that iontophoresis application enhanced the skin penetration of imatinib mesylate
loaded AuNP by 6.2-fold compared with passive application.
Bessar et  al. [67] prepared water-soluble sodium 3-mercapto1-propansulfonate(3MPS)-capped AuNPs, which were loaded with methotrexate (MTX) via electrostatic adsorption. The resulting Au-3MPS@MTX conjugate
showed an average size and a zeta-potential of ~5 nm and −32 ± 1 mV, respectively.
It was then administrated topically on C57BL/6 mouse normal skin in order to assess
its absorption behaviour. In vitro and in vivo studies showed that MTX-conjugated
AuNPs were much more efficient than MTX alone, suggesting this nanosystem as a
potential candidate for topical treatment of psoriasis (see Fig. 4A).
An interesting application of bioconjugated plasmonic NPs for enhanced transdermal gene delivery was the reported by Niu and co-workers [69]. In order to
facilitate the skin penetration of plasmid DNA (i.e., pDNA encoding miRNA-221
inhibitor -Mi221-) deep into melanoma tissues, these authors synthesized 20–25 nm
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