Periodontitis is a complex disease and bacterial infection is one of the most common factors involved in this disease. Current strategies for the local delivery of antibiotics do not allow a complete clearance of bacteria filling dentinal tubules and this limits their therapeutic efficacy. Therefore, there is a strong need for the development of new delivery strategies aimed at improving the efficacy of antibiotic therapy for periodontitis with special reference to their ability to penetrate into the tubules. The aim of the present study is to develop liposome-based delivery systems of sub-micron dimension, able to diffuse into the dentinal tubules. A further aim of the research is to develop a protocol for enhanced diffusion based on the use of magnetic liposomes and magnetic fields. Liposomes were produced by hydration of a pre-liposomal formulation. The vesicles were stabilised with PEG and their re-sizing was achieved by extrusion. Magnetite nanoparticles were synthesized inside the vesicles, i.e., the chemical reaction involving FeCl₂, FeCl₃ and NH₃ occurred within the core of the newly formed liposomes. Dynamic light scattering analysis was performed for size characterization. A mathematical model was implemented to predict the diffusion of the liposomes in dentinal tubules. Ex-vivo validation was performed on extracted human teeth. We produced PEG-ylated liposomes (average size 204.3 nm) and PEG-ylated magnetic liposomes (average size 286 nm) and an iron content of 4.2 μg/ml. Through mathematical modelling, we deduced that sub-micrometer vesicles are able to penetrate into dentinal tubules. This penetration is considerably more effective when the vesicles are magnetized and subjected to an external magnetic field which accelerates their movement within the tubules. The liposome-based delivery systems developed by the present study are able to penetrate deeply into the tubules, sometimes reaching their terminal ends.