Review Article
Interaction of inorganic nanoparticles with the skin barrier: current status and critical review

https://doi.org/10.1016/j.nano.2012.04.004Get rights and content

Abstract

Integration of nanotechnology with biology leads to various advantages in applied pharmaceutical and medical sciences. In that regard, the behavior of nanoparticles (NPs) in relation to the skin, an important biological barrier, has been the target of several recent studies. Yet the potential ability of NPs to penetrate into the underlying viable tissue lies at the center of debate. This review briefly highlights the current applications of inorganic NPs, then discusses the current status of their skin penetration in view of the vast variation among the experimental setups in use. Determinants of particle penetration, adopted approaches for enhanced penetration, the underlying mechanism, as well as qualitative and quantitative analysis of NPs present in the skin are also within the scope of this review article. We emphasize analyzing the data generated from experiments on human skin, the “gold standard” for assessment of in vitro skin penetration. Based on this, we include some recommendations for future research.

From the Clinical Editor

Transdermal application of inorganic nanoparticle-based medications is of growing interest in nanomedicine research. This critical review discusses the knowns and the unknowns of this field, providing insightful recommendations for future research.

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).

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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:

  • Human skin should be used as the first-choice “gold standard” skin model for in vitro penetration

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    No conflict of interest was reported by the authors of this paper.

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