Effects of oligonucleotide adsorption on the physicochemical characteristics of a nanoparticle-based model delivery system for antisense drugs

Cationic polystyrene nanoparticles, as a model drug carrier system for nucleic acids, are capable of binding negatively charged oligonucleotides by multiple electrostatic interactions. The effect of the adsorption of phosphorothioate oligonucleotides on the physicochemical properties of the carrier system was investigated for uncoated and sterically stabilized latex particles. Turbidity measurements and photon-correlation spectroscopy indicate that the colloidal stability of the nanoparticle-oligonucleotide conjugates is influenced by the number of oligonucleotides adsorbed on the carrier. Especially in the case of the uncoated material, a destabilizing effect has been observed up to oligonucleotide concentrations of 2.7 μmol/g polymer. Strikingly, at higher concentrations the latexes exhibit colloidal stability similar to the oligonucleotide-free samples. These results were correlated to zeta-potential measurements demonstrating a reversal from positive to negative values of the zeta potential with increasing oligonucleotide concentration. The points of zero charge of the particles are in the region of maximum coagulation. These findings were compared to adsorption studies and calculations based on the random sequential adsorption model. It appears that at first the colloidal stability of the carrier systems is diminished with increasing oligonucleotide adsorption, while higher surface coverages lead to a significant reduction in coagulation. At the saturation level the surface coverage can be considered as a monolayer of “side-on” adsorbed molecules and the conjugates exhibit colloidal stability similar to the bare particles without adsorbed molecules. Received: 20 April 1998 Accepted: 16 July 1998