The goal of this study was the evaluation of albumin nanoparticles as drug delivery systems for antisense oligonucleotides. Bovine serum albumin (BSA) nanoparticles were prepared by a coacervation process. A phosphodiester oligonucleotide was either incorporated into the matrix of the particles by incubation with the albumin prior the coacervation process or adsorbed onto the pre-formed nanoparticles. Incorporated and/or adsorbed oligonucleotide was estimated by capillary electrophoresis and fluorescence spectroscopy. The adsorbed amount of oligonucleotide was dramatically dependent on the pH of the medium. Desorption of the oligonucleotide was also affected by the pH and ionic strength of the medium. This indicated that electrostatic forces play a major role in the interaction between the oligonucleotide and the nanoparticles. When the oligonucleotide was incubated with the albumin prior to nanoparticle formation, the profile of release confirmed that a fraction was incorporated into the matrix and its release was controlled by the albumin degradation. The hybridisation capability of the oligonucleotide in both nanoparticle formulations was retained. However, only the oligonucleotide incorporated into the nanoparticle matrix was protected against enzymatic degradation.