Transmucosal delivery emerged as a promising strategy to improve the pharmacokinetics of drugs. The engineering of drug nanocarriers that combine fine-tuned mucoadhesive and mucopenetrating features is currently being investigated to ensure a more efficient mucosal delivery of the active agents. Our research group developed a new family of amphiphilic nanogels based on the non-covalent crosslinking of self-assembly nanoparticles. In this work, we report on the synthesis of nanoparticles made of chitosan-g-poly(methyl methacrylate) (CS-g-PMMA) copolymers that were surface-modified with two types of thiol residues, namely N-acetyl cysteine and 3-mercaptopropionic acid. The critical micellar concentration was in the 0.03-0.06% w/v range, as measured by dynamic light scattering. The nanoparticles ionotropically crosslinked with tripolyphosphate showed very good cell compatibility in Caco2 and HT29-MTX cell lines in 0.05%-0.1% w/v range after 4-48 h. Finally, their permability was characterized in a model of intestinal mucosa in vitro.