¹Department of Pharmaceutical Technology, Faculty of Pharmacy, Ankara University, Ankara, Turkey DOI : 10.35333/jrp.2019.38 S-adenosyl-L-methionine (SAMe) is an endogenic methyl donor naturally present in all living cells; it has high water solubility, but its bioavailability is low in oral administration due to the first pass effect in the liver. The aim of this study is to prepare colon targeted chitosan nanoparticles containing SAMe by ionic gelation. In the preparation of the formulations, the effects of chitosan concentration, tripolyphosphate (TPP) concentration and the amount of SAMe on the specifications of the nanoparticles such as particle size, zeta potential, encapsulation efficiency, and process yield, were investigated. Drug-excipient interactions were evaluated by differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. The obtained nanoparticles showed bimodal particle size distribution ranging between 228.3-763.9 nm and their zeta potentials were within 14.10-23.30 mV. The drug encapsulation efficiencies and process yields of the nanoparticles were low. However, when the effects of the process parameters on the characteristics of nanoparticles were examined, the chitosan concentration and SAMe amount were significant parameters affecting particle size. The chitosan concentration was also found to have a significant effect on process yield (p <0.05). Drug release from nanoparticles was evaluated according to different kinetic models and it was found that the release mechanism was Fickian diffusion. Keywords : S-adenosylmethionine; chitosan; nanoparticle; colon; bioavailibility