Penetration of Gold Nanoparticles through Human Skin: Unraveling Its Mechanisms at the Molecular Scale.

Recent experimental studies suggest that nanosized gold nanoparticles (AuNPs) are able to penetrate into the deeper layer (epidermis and dermis) of rat and human skin. However, the mechanisms by which these AuNPs penetrate and disrupt the skin's lipid matrix are not well understood. In this study, we have used computer simulations to explore the translocation and the permeation of AuNPs through the model skin lipid membrane using both unconstrained and constrained coarse-grained molecular dynamics simulations. Each AuNP (1-6 nm) disrupted the bilayer packing and entered the interior of the bilayer rapidly (within 100 ns). It created a hydrophobic vacancy in the bilayer, which was mostly filled by skin constituents. Bigger AuNPs induced changes in the bilayer structure, and undulations were observed in the bilayer. The bilayer exhibited self-healing properties; it retained its original form once the simulation was run further after the removal of the AuNPs. Constrained simulation results showed that there was a trade-off between the kinetics and thermodynamics of AuNP permeation at a molecular scale. The combined effect of both resulted in a high permeation of small-sized AuNPs. The molecular-level information obtained through our simulations offers a very convenient method to design novel drug delivery systems and effective cosmetics.