Effects on Nanoparticle Size and Functionalization on Skin Penetration, Cellular Uptake and Cytotoxicity

  • Fiorenza Rancan, Clinical Research Center for Hair and Skin Science, Department of Dermatology , Charité-Universitaetsmedizin Berlin, Germany
  • Stefan Troppens, Clinical Research Center for Hair and Skin Science, Department of Dermatology , Charité-Universitaetsmedizin Berlin, Germany
  • Qi Gao Christina Graf, Physikalische Chemie, Institut für Chemie und Biochemie Freie Universität Berlin, Germany
  • Martina Meinke, Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology , Charité-Universitaetsmedizin Berlin, Germany
  • Eckhart Ruehl, Germany
  • Jürgen Lademann, Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology , Charité-Universitaetsmedizin Berlin, Germany
  • Ulrike Blume-Peytavi, Clinical Research Center for Hair and Skin Science, Department of Dermatology , Charité-Universitaetsmedizin Berlin, Germany
  • Annika Vogt, Clinical Research Center for Hair and Skin Science, Department of Dermatology, Charité-Universitaetsmedizin Berlin, Germany

Nanoparticles (NPs) are increasingly employed in commercial and medical products and there is growing interest in the use of NP for targeted drug delivery. However, investigations on NP-cell interactions and possible hazardous effects related to NP-skin contact are especially important in the light of our recent results on NP penetration in barrier-disrupted human skin.
Because of their easy and low-cost production silica NPs are widely used in paints as well as in diagnostics and drug delivery research. The aim of this study was to systematically investigate the effects of NP size and surface modifications on skin penetration, cellular uptake, as well as NP-associated cytotoxicity and induction of oxidative stress in human skin explants, cell lines and primary skin cells. Silica particles ranging from 42 to 300nm were internalized by HaCaT cells within 2 hours of incubation indicating that the uptake ability of these cells is not limited by the particle size. Similar results were found for Langerhans cells isolated from excised human skin whereas freshly isolated keratinocytes showed much lower uptake abilities. Silica particles functionalized with positively charged amino groups displayed a better uptake than the un-functionalized particles. We found a dose dependent increase of cytotoxicity within a concentration range of 10-100 µg/ml. Interestingly, particles <100nm showed higher toxicity than particles ranging between 200nm and 300nm in size. The penetration experiments on excised human skin revealed that 75nm and 42nm silica particles penetrated into the hair follicles but only the smallest translocated into the epidermis and were associated with keratinocytes and Langerhans cells, independently on their functionalization.
We can conclude that particle size and functionalization can strongly influence the in vitro particle uptake. Particles <100nm exhibited higher cytotoxicity than larger particles, which is especially important, because particle size was also the major determinant for particle translocation across the skin barrier.