The goals of the project are (i) acute and chronic local, regional and systematic tracing of functionalized particles following topical application to the skin, (ii) histological and molecular characterization of local and systemic cellular responses, (iii) histological comparison of ex vivo skin models: mouse, pig, cow, human, (iv) effects of ulcerative skin diseases on particle uptake, distribution and cellular and tissue responses in mouse models. Work program consists of (i) characterization of the local penetration and systemic distribution of surface functionalized SiO2 nanoparticles of different shapes and sizes in mouse skin models, (ii) comparison of ex vivo cow and pig skin models with mouse and human skin, (iii) mouse model of epithelial barrier defects: influence on particle distribution and tissue reaction patterns