In the present study, oligonucleotides were adsorbed onto the surface of cationic liposomes and nanoparticles at different ratios. As a result, the surface charges of the colloidal carriers were decreased with increasing oligonucleotide concentration. At a certain oligonucleotide concentration, complete charge neutralization led to the aggregation of the carrier systems. Further increasing oligonucleotide concentrations reversed the surface charge of liposomes and nanoparticles to a negative one. Ultrasonication was investigated as a possible means for the homogenization of the formed aggregates. However, the use of ultrasonication led to a time-dependent damage of oligonucleotides adsorbed onto AH-Chol liposomes and MMAEMC-nanoparticles, as well as of unbound oligonucleotides. Nearly 60% of the oligonucleotides adsorbed to MMAEMC-nanoparticles and 65% of ODNs adsorbed to the liposomes were degraded by the effect of cavitation produced by ultrasonication within 10 min. In contrast, the oligonucleotides were protected from degradation when DEAE-stabilized PHCA-nanoparticles were employed as ODN carriers. More than 80% of the oligonucleotides entangled in the surface matrix of these nanoparticles remained intact.