The delivery of nucleic acids via the oral route involves overcoming barriers such as degradation of nucleic acids by low pH in the stomach, enzymatic degradation by DNases in the gut, crossing the physical barrier imposed by the mucus layer, cellular uptake, intracellular trafficking and nuclear uptake. As an oral drug carrier system chitosan nanoparticles are ideal, being mucoadhesive, interacting with the anionic sialic acid residues in mucin. In this study, plasmid DNA expressing a humanized secreted Gaussia Luciferase as reporter gene was encapsulated in alginate and chitosan nanoparticles, via a mild ionotropic gelation procedure with sodium tripolyphosphate as a counterion. The nanoparticle system here developed shows effective transfection of different human gastric epithelial cell lines with distinct cell differention. That was confirmed by the expression of luciferase in the different tested conditions, particularly the amount of encapsulated pGLuc.