The aim of this study was to generate a new type of nanoparticles made of chitosan (CS) and carboxymethyl-beta-cyclodextrin (CM-beta-CD) and to evaluate their potential for the association and delivery of macromolecular drugs. CS and CM-beta-CD or mixtures of CM-beta-CD/tripolyphosphate (TPP) were processed to nanoparticles via the ionotropic gelation technique. The resulting nanoparticles were in the size range of 231-383 nm and showed a positive zeta potential ranging from +20.6 to +39.7 mV. These nanoparticles were stable in simulated intestinal fluid pH 6.8 at 37 degrees C for at least 4h. Elemental analysis studies revealed the actual integration of CM-beta-CD to CS nanoparticles. Insulin and heparin used as macromolecular model drugs, could be incorporated into the different nanocarriers with association efficiencies of 85.5-93.3 and 69.3-70.6%, respectively. The association of these compounds led to an increase of the size of the nanoparticles (366-613 nm), with no significant modification of their zeta potentials (+23.3 to +37.1 mV). The release profiles of the associated macromolecules were highly dependent on the type of molecule and its interaction with the nanomatrix: insulin was very fast released (84-97% insulin within 15 min) whereas heparin remained highly associated to the nanoparticles for several hours (8.3-9.1% heparin within 8h). In summary, CS-CD (cyclodextrin) nanoparticles may be considered as nanocarriers for the fast or slow delivery of macromolecules.