Review ArticleInteraction of inorganic nanoparticles with the skin barrier: current status and critical review
Graphical Abstract
Nanoparticles could remain on the skin surface (1), penetrate into the skin through intercellular pathways and localize in the stratum corneum (2) or even permeate the whole stratum corneum into deeper skin layers (3). On the other hand, hair follicles could act as a depot for particles (4) from where particles could further penetrate into deeper skin layers (5).
Section snippets
Quantum dots (QDs)
QDs are nanocrystals composed of a semiconductor material (e.g., CdS). QDs have attracted widespread interest in biology and medicine because of their unique electronic and optical properties in relation to organic dyes and fluorescent proteins, including size- and composition-tunable emission wavelength, improved signal-to-noise ratio, and higher photostability. Therefore, QDs have rapidly emerged as a new class of fluorescent probes for biomolecular and cellular imaging.7, 8 Surface
Significance and scope of the review article
One could thus far conclude that inorganic NPs have found several applications, especially in cancer diagnosis and therapy, and more recently in drug and gene delivery. This potential for applications has triggered the investigation of the NP interaction with the various biological barriers. An excellent biological barrier, the skin, has been addressed in several recent studies regarding NP penetration.
Skin, a unique barrier composed of several highly organized and heterogeneous layers, also
Current dilemma in the status of skin penetration of inorganic NPs
Investigating the ability and the possible mechanism of particle penetration through skin is a recent area of research receiving great interest of researchers for the reasons already mentioned. Starting from the year 2004, the number of studies focusing on skin penetration of inorganic particles is generally increasing. To the best of our knowledge, the total number of research articles in this field is 40 (excluding replicate studies common in skin penetration/permeation experiments), in which
Factors affecting skin penetration
In addition to the aforementioned experimental variations among different studies, several factors were systematically studied and found to contribute significantly in the skin penetration by NPs. Critical determinants of NP skin penetration include physicochemical attributes of the NPs (size, surface charge, surface chemistry, and physical state of the nanodispersion on coming in contact with the skin surface), formulation factors (vehicle), and experimental factors (concentration and skin
Approaches adopted to enhance skin penetration by inorganic NPs
There is no study that systematically investigates the possibilities of enhancement of particle penetration. Some approaches were, however, adopted to enhance skin penetration of inorganic NPs. Most of these approaches were physical methods. Yet, the use of chemical enhancers was also explored.
Mechanism of skin penetration
The exact contribution of the relevant parameters for potential skin penetration of inorganic NPs is still unknown. Studying the skin architecture could provide a possible explanation for the skin penetration of NPs. The intercellular lipids in the SC arrange themselves in a head-to-head and a tail-to-tail manner. The lipophilic pores are formed by tail-to-tail configuration of the lipids. On the other hand, the aqueous pores are hydrophilic regions delimited by lipid heads.103 Although the
Penetration of inorganic NPs through human skin: dissecting the nano effect
Whether particle penetration is studied for risk assessment or drug delivery purposes, the basic knowledge of the underlying mechanisms is an essential aspect. For NPs the size is the most prominent parameter. Hence the contribution and importance of the particle size has always faced several difficulties.
Following in vivo studies on human volunteers (difficult to perform), excised human skin is regarded as the “gold standard” for in vitro skin penetration studies, especially in human dermal
Qualitative and quantitative analysis of inorganic NPs in the skin
The rapid development of sensitive analytical techniques in the past decades has enabled researchers to monitor and accurately quantify the amount of drugs present in the skin after penetration/permeation experiments, and study the factors that either hinder or enhance their penetration. Among these techniques, high-pressure liquid chromatography provides a convenient method with a suitable limit of detection for accurate drug quantitation. On the other hand, quantitation of NPs often
Standpoint and recommendations for future directions
Applications of inorganic NPs in pharmaceutical and biomedical fields have been established and are increasing progressively. Yet, the behavior of NPs with respect to the skin barrier is still in question with several conflicting results reported in the literature. In an attempt to solve this dilemma some points should be taken into consideration as recommendations for future investigations:
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Human skin should be used as the first-choice “gold standard” skin model for in vitro penetration
References (120)
Why do we have so many definitions for nanoscience and nanotechnology?
Nanomed Nanotechnol Biol Med
(2010)What is nanotechnology?
Applications of nanotechnology in dermatology
J Invest Dermatol
(2012)- et al.
Tailor-made biofunctionalized nanoparticles using layer-by-layer technology
Int J Pharm
(2010) - et al.
Review: bioanalytical applications of biomolecule-functionalized nanometer-sized doped silica particles
Anal Chim Acta
(2009) - et al.
Effect of silver on burn wound infection control and healing: review of the literature
Burns
(2007) - et al.
Silver nanoparticles as a new generation of antimicrobials
Biotechnol Adv
(2009) - et al.
Biological properties of “naked” metal nanoparticles
Adv Drug Deliv Rev
(2008) - et al.
Au nanoparticles target cancer
Nano Today
(2007) - et al.
Gold nanoparticles in delivery applications
Adv Drug Deliv Rev
(2008)
The forthcoming applications of gold nanoparticles in drug and gene delivery systems
J Control Release
Magnetically modulated therapeutic systems
Int J Pharm
The safety of nanosized particles in titanium dioxide– and zinc oxide–based sunscreens
J Am Acad Dermatol
New insights into skin structure: scratching the surface
Adv Drug Deliv Rev
Nanotechnology and the transdermal route: a state of the art review and critical appraisal
J Control Release
Distribution of sunscreens on skin
Adv Drug Deliv Rev
The influence of corneocyte structure on the interpretation of permeation profiles of nanoparticles across skin
Nuclear Instrum Meth Phys Res B
Investigations of percutaneous uptake of ultrafine TiO2 particles at the high energy ion nanoprobe LIPSION
Nuclear Instrum Meth Phys Res B
The in vitro absorption of microfine zinc oxide and titanium dioxide through porcine skin
Toxicol in Vitro
Toxicity and penetration of TiO2 nanoparticles in hairless mice and porcine skin after subchronic dermal exposure
Toxicol Lett
On the follicular pathway of percutaneous uptake of nanoparticles: ion microscopy and autoradiography studies
Nuclear Instrum Meth Phys Res B
Nuclear microprobe study of TiO2-penetration in the epidermis of human skin xenografts
Nuclear Instrum Meth Phys Res B
In vitro permeation of gold nanoparticles through rat skin and rat intestine: effect of particle size
Colloids Surf B
Transdermal skin delivery: predictions for humans from in vivo, ex vivo and animal models
Adv Drug Deliv Rev
Assessment of penetration of quantum dots through in vitro and in vivo human skin using the human skin equivalent model and the tape stripping method
Biochem Biophys Res Commun
The human epidermis models EpiSkin®, SkinEthic® and EpiDerm®: an evaluation of morphology and their suitability for testing phototoxicity, irritancy, corrosivity, and substance transport
Eur J Pharm Biopharm
Co-administration of protein drugs with gold nanoparticles to enable percutaneous delivery
Biomaterials
Skin absorption: flow-through or static diffusion cells
Toxicol in Vitro
Characterization of the iontophoretic permselectivity properties of human and pig skin
J Control Release
Influence of different ceramides on the structure of in vitro model lipid systems of the stratum corneum lipid matrix
Chem Phys Lipids
Penetration of metallic nanoparticles in human full-thickness skin
J Invest Dermatol
Biophysical and morphological changes in the stratum corneum lipids induced by UVB irradiation
J Dermatol Sci
Enhanced transdermal-immunization with diphtheria-toxoid using local hyperthermia
Vaccine
Enhanced skin permeation of naltrexone by pulsed electromagnetic fields in human skin in vitro
J Pharm Sci
Low-frequency sonophoresis: current status and future prospects
Adv Drug Deliv Rev
Low-frequency sonophoresis: ultrastructural basis for stratum corneum permeability assessed using quantum dots
J Invest Dermatol
Effects of ultrasound and sodium lauryl sulfate on the transdermal delivery of hydrophilic permeants: comparative in vitro studies with full-thickness and split-thickness pig and human skin
J Control Release
Selective removal of stratum corneum by microdermabrasion to increase skin permeability
Eur J Pharm Sci
Lasers and microdermabrasion enhance and control topical delivery of vitamin C
J Invest Dermatol
Effects of relative humidity and ambient temperature on the ballistic delivery of micro-particles to excised porcine skin
J Invest Dermatol
Thermal scalpel to target cancer
Expert Rev Med Devices
Nanotechnology-Big things from a tiny world
Review: biofunctionalized quantum dots in biology and medicine
J Nanomater
Application of quantum dots–based biotechnology in cancer diagnosis: current status and future perspectives
J Nanomater
In vivo cancer targeting and imaging with semiconductor quantum dots
Nat Biotechnol
Quantum dots for live cells, in vivo imaging, and diagnostics
Science
Bioconjugated silica nanoparticles: development and applications
Nano Res
Cytotoxicity and immunological response of gold and silver nanoparticles of different sizes
Small
The bactericidal effect of silver nanoparticles
Nanotechnology
Silver nanoparticles—the real “silver bullet” in clinical medicine?
Med Chem Comm
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