Chitosan/cyclodextrin nanoparticles as macromolecular drug delivery system

Abstract

The aim of this study was to generate a new type of nanoparticles made of chitosan (CS) and carboxymethyl-β-cyclodextrin (CM-β-CD) and to evaluate their potential for the association and delivery of macromolecular drugs. CS and CM-β-CD or mixtures of CM-β-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 °C for at least 4 h. Elemental analysis studies revealed the actual integration of CM-β-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 8 h). In summary, CS-CD (cyclodextrin) nanoparticles may be considered as nanocarriers for the fast or slow delivery of macromolecules.