The influence of the surface functionalization of silica particles on their colloidal stability in physiological media is studied and correlated with their uptake in cells. The surface of 55 ± 2 nm diameter silica particles is functionalized by amino acids or amino- or poly(ethylene glycol) (PEG)-terminated alkoxysilanes to adjust the zeta potential from highly negative to positive values in ethanol. A transfer of the particles into water, physiological buffers, and cell culture media reduces the absolute value of the zeta potential and changes the colloidal stability. Particles stabilized by L-arginine, L-lysine, and amino silanes with short alkyl chains are only moderately stable in water and partially in PBS or TRIS buffer, but aggregate in cell culture media. Nonfunctionalized, N-(6-aminohexyl)-3-aminopropyltrimethoxy silane (AHAPS), and PEG-functionalized particles are stable in all media under study. The high colloidal stability of positively charged AHAPS-functionalized particles scales with the ionic strength of the media, indicating a mainly electrostatical stabilization. PEG-functionalized particles show, independently from the ionic strength, no or only minor aggregation due to additional steric stabilization. AHAPS stabilized particles are readily taken up by HeLa cells, likely as the positive zeta potential enhances the association with the negatively charged cell membrane. Positively charged particles stabilized by short alkyl chain aminosilanes adsorb on the cell membrane, but are weakly taken up, since aggregation inhibits their transport. Nonfunctionalized particles are barely taken up and PEG-stabilized particles are not taken up at all into HeLa cells, despite their high colloidal stability. The results indicate that a high colloidal stability of nanoparticles combined with an initial charge-driven adsorption on the cell membrane is essential for efficient cellular uptake.

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In this study, the skin penetration and cellular uptake of amorphous silica particles with positive and negative surface charge and sizes ranging from 291 ± 9 to 42 ± 3 nm were investigated. Dynamic light scattering measurements and statistical analyses of transmission electron microscopy images were used to estimate the degree of particle aggregation, which was a key aspect to understanding the results of the in vitro cellular uptake experiments. Despite partial particle aggregation occurring after transfer in physiological media, particles were taken up by skin cells in a size-dependent manner. Functionalization of the particle surface with positively charged groups enhanced the in vitro cellular uptake. However, this positive effect was contrasted by the tendency of particles to form aggregates, leading to lower internalization ratios especially by primary skin cells. After topical application of nanoparticles on human skin explants with partially disrupted stratum corneum, only the 42 ± 3 nm particles were found to be associated with epidermal cells and especially dendritic cells, independent of their surface functionalization. Considering the wide use of nanomaterials in industries and the increasing interest for applications in pharmaceutics and cosmetics versus the large number of individuals with local or spread impairment of the skin barrier, e.g., patients with atopic dermatitis and chronic eczema, a careful dissection of nanoparticle-skin surface interactions is of high relevance to assess possible risks and potentials of intended and unintended particle exposure.

Recent advances in the field of nanotechnology have allowed the manufacturing of elaborated nanometer-sized particles for various biomedical applications. A broad spectrum of particles, extending from various lipid nanostructures such as liposomes and solid lipid nanoparticles, to metal, nanocrystalline and polymer particles have already been tested as drug delivery systems in different animal models with remarkable results, promising an extensive commercialization in the coming years. Controlled drug release to skin and skin appendages, targeting of hair follicle-specific cell populations, transcutaneous vaccination and transdermal gene therapy are only a few of these new applications. Carrier systems of the new generation take advantage of improved skin penetration properties, depot effect with sustained drug release and of surface functionalization (e.g., the binding to specific ligands) allowing specific cellular and subcellular targeting. Drug delivery to skin by means of microparticles and nanocarriers could revolutionize the treatment of several skin disorders. However, the toxicological and environmental safety of micro- and nanoparticles has to be evaluated using specific toxicological studies prior to a wider implementation of the new technology. This review aims to give an overview of the most investigated applications of transcutaneously applied particle-based formulations in the fields of cosmetics and dermatology.