The design of bioadhesive nanoparticles (NPs) for targeting specific sites within the gut remains a major challenge. One possible strategy to solve this problem may be the use of pegylated NPs. In general, these carriers display different bioadhesive properties to nondecorated NPs. Thus, pegylated NPs show a higher ability to interact with the small intestine mucosa rather than with the stomach. However, the type of surface conformation of polyethylene glycol chains appears to have a great influence on the behaviour of these NPs. Theoretically, the traditional 'brush' polyethylene glycol corona would facilitate the penetration of the pegylated particles through the mucus layer and the subsequent adhesive interaction with the mucosa, which would promote their absorption by intestinal enterocytes. On the contrary, pegylated NPs with a 'loop' conformation would increase the time of residence of the adhered fraction of particles in the mucosa.