This initiative aims to gain both fundamental understanding and applied knowledge on novel polysaccharide-based nanoparticles to be utilized as ‘smart’ advanced delivery systems of therapeutic biomacromolecules for oral administration. To this end, nanoparticles will be harnessed from chitosan and other polyionic polysaccharides of biomedical use, cross-linked with a natural non-toxic biocompatible agent. Sensitivity to changes in temperature and pH will be conferred by modifying the surface charge (zeta potential) by modifying the local hydrophilic/hydrophobic balance the nanoparticle surface. While sensitivity towards two biomolecules of therapeutic significance will be achieved by modifying the nanoparticle surface by molecular imprinting, using a non-covalent approach. Phase transitions in these systems will be investigated by means of biophysical techniques including dynamic light scattering and SAXS (small-angle X-ray scattering). The adsorption capacity and selectivity of the molecularly imprinted surface will be studied by quartz crystal micro balance with dissipation mode (QCM-D) techniques. The in vitro release profile will be evaluated as a function of the presence of the external stimuli (temperature, pH and concentration of specific molecules). Citotoxicity and cell uptake will be evaluated in Caco-2 cell monoculture and the biopharmaceutical performance will be evaluated for selected prototypes after oral administration in a rat model.the biopharmaceutical performance will be evaluated after oral administration in a rat model.