¹Department of Pharmaceutical Technology, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey DOI : 10.35333/jrp.2019.37 The aim of this study was to formulate Lamivudine (LAM) loaded poly lactic-co-glycolic acid (PLGA) nanoparticle (NP) formulations by ‘double emulsion solvent evaporation’ method for oral administration. PLGA with similar molecular weight but two different chemical end-groups (acid or ester terminated), were used in this study to to compare the effects in the characterization of NPs. Particle size (PS), polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), dissolution and release kinetic studies were carried out for the characterization of NPs and finally for determining the optimum formulation. The selected optimum formulation (B coded) was found to have a PS of 221.00.7 nm and a low PDI as 0.1040.014. Drug EE % of optimal NP formulation was found as 30.280%0.600. In vitro release of LAM loaded NPs were examined in phosphate buffer (pH 6.8). In vitro release studies of LAM-loaded NPs showed an extended release up to 144 hours, thus the demonstration of nanostructures was confirmed. Higuchi and Korsmeyer-Peppas kinetic model was found to fit best for LAM release from PLGA-NPs. The optimum formulation was stable in the 24-hour gastrointestinal stability study and the NP structure was characterized by DSC, FT-IR and 1HNMR analyzes. It could be concluded that LAM loaded NPs seem to be a promising extended release drug delivery system for oral administration in antiretroviral therapy. Lastly, in vitro characterization and release data demonstrated the possibility of improved bioavailability of LAM by PLGA-NP formulation and the effect of polymers used in this study on formulation characteristics were also elucidated. Keywords : Lamivudine; nanoparticle; PLGA; ester terminated PLGA; acid terminated PLGA; polymer; release kinetics; antiretroviral therapy