Lipid-based particles (Cubosome particles) were surface-modified by chitosan and the ratio between particles and chitosan was optimized to minimize the free chitosan concentration in the dispersion. The modified particles were characterized by electrophoretic measurements and the pH dependence of the zeta potential could be directly related to the protonation of chitosan. Interaction between the modified particles and mucin-coated silica surfaces were subsequently investigated in situ by ellipsometry to assess the mucoadhesive properties at physiologically relevant conditions. The result showed that a substantial amount of modified particles was adsorbed to mucin-coated silica surfaces at both pH 4 and pH 6, probably due to electrostatic interactions between amino groups in chitosan and negatively charged groups in mucin. Furthermore, the amount of bound particles decreased by less than 15% upon rinsing indicating relatively strong interactions. This investigation demonstrates that ellipsometry is a useful tool to study mucoadhesive properties of particles in the submicrometer range. Moreover, the novel chitosan-modified particles may be of interest for mucosal drug delivery applications.