Nanoparticles (NP) are known for their specific accumulation in the inflamed tissues in the colon and may therefore allow a selective delivery to the site of inflammation including a reduction of adverse effects. 5-amino salicylic acid (5ASA) loaded NP were designed in order to investigate their therapeutic potential in the treatment of inflammatory bowel disease. 5ASA was covalently bound to poly(caprolactone) prior to all formulation steps. Oil/water emulsification or nanoprecipitation methods were used for the NP formulation. Particle diameters were either 200 or 350 nm for emulsification or nanoprecipitation, respectively. In-vitro drug release demonstrated a significant drug retention inside the NP formulation. Toxicity of the different formulations was evaluated on Caco-2 and HEK cell culture which was slightly increased for 5ASA grafted NP in comparison to blank NP (Me5ASA-NP: 75 microg/l; blank NP: 210 microg/l). In-vivo, clinical activity score and myeloperoxidase activity decreased after administration of all 5ASA containing formulations (untreated control: 28.0+/-5.6 U/mg; 5ASA-NP (0.5 mg/kg): 15.2+/-5.6 U/mg; 5ASA solution (30 mg/kg): 16.2+/-3.6 U/mg). NP formulations allowed to lower significantly the dose of 5ASA. These oral NP formulations demonstrated their therapeutic potential and appear to be an interesting approach for the therapy of inflammatory bowel disease.