Nanotechnology is considered as the most innovative and revolutionary technology of the 21st century. The increasing use of nanomaterials in consumer products raises questions of potential harmful effects on humans and the environment. In this study the penetration behavior of different titanium dioxide nanoparticles was evaluated dependent on the physicochemical properties. Furthermore, an advanced buccal in-vitro model was developed to get a basic understanding of particle/cell interactions. The physicochemical properties (i.e., size, surface hydrophobicity) of the particles were characterized with PCS, LD and TEM. The particles were dispersed in different media and sonicated. Ex-vivo permeability tests were conducted with excised porcine buccal mucosa using Franz diffusion cells. To investigate potential cytotoxic effects of the particles, MTS and LDH assays were performed on an oral cell line (i.e., TR 146). For the development of an advanced buccal in-vitro model, different mucins were characterized (FTIR, SEM) and an external mucinlayer was combined with confluent cell layers. The results of the particle characterization showed that the particle size highly depends on the dispersion medium, the treatment and the measurement technology. Electron microscopy demonstrated that NM 100 particles with a predominant size of 148 nm and a slightly hydrophilic surface (K = 0,099) penetrated in deep regions of the epithelium. The results of the in-vitro toxicity tests showed an increased mitochondrial activity (NM103 and NM105) and an affected integrity of the cell membrane (NM102 and NM105). The chemical and morphological evaluation of the in-vitro model demonstrated that porcine mucin is most similar to human mucin. The adherence of mucin fibers onto the cell surface could be demonstrated and the viability of the model was maintained at least for 48 h. Finally, transport studies with model-particles showed that this model is suitable to simulate the human buccal mucosa.