A novel method was used to synthesize cholic acid hydrophobic-modified dextrans (CAH-Dex) which form nanoparticles in aqueous solution. The stabilization and drug-loading of the formed nanoparticles were investigated. Dextran was oxidized by sodium periodate to dextran dialdehyde which was then conjugated with cholic acid hydrazide through an acyl hydrazone linkage. The self-aggregation behavior of the resulting conjugates was investigated using nuclear magnetic resonance, fluorescence and photo correlation spectrometry. The conjugates were found to have low critical aggregate concentrations (CAC) (0.46-0.96 x 10(-2) mg mL(-1)) which is characteristic, depending on both the oxidization and substitution degrees. Above the CAC the conjugates tend to form nanoparticle aggregates with inner hydrophobic environment. The diameters of the nanoparticles rely on the pH of the medium due to the aldo-enol transition of the dextran dialdehyde. By crosslinking the aldehyde groups located on the surface using adipic dihydrazide, the nanoparticles were obviously stabilized. The drug-loading and release behavior of the nanoparticles was investigated using indomethacin as a hydrophobic model drug. (c) 2006 Society of Chemical Industry.