Nowadays, the application of green chemistry principles in the production of new polymeric materials is receiving an increasing attention. In the present work, we have investigated the impregnation of chitosan with lactulose using supercritical fluids under various operating conditions, in order to improve the solubility of this natural polymer at neutral or basic pH. A comparison between chitosan scaffolds and microspheres is also presented; both chitosans were characterized using scanning electron microscopy (SEM), mercury intrusion porosimetry (MIP) and Fourier transform infrared spectroscopy (FTIR). The degree of impregnation was evaluated by quantitative gas chromatography (GC-FID) analysis and interactions chitosan-lactulose by ninhydrin method. The supercritical carbon dioxide impregnation proved to be feasible for both chitosan forms. The highest impregnation yield (8.6%) was obtained for chitosan scaffolds using the following impregnation parameters: continuous process, 60 min contact time, 14% (v/v) of co-solvent ethanol:water (95:5), depressurization rate equal to 3.3 bar/min, 100 bar of pressure and 100 degrees C. Under these conditions, Maillard reaction also occurred. (C) 2011 Elsevier B.V. All rights reserved.