Nanoparticle DNA Carrier with Poly(l-lysine) Grafted Polysaccharide Copolymer and Poly(d,l-lactic acid)

Abstract

Biodegradable nanoparticles, which contain the sites for both polynucleotide adsorption and targeting ligand on their surfaces, were prepared as a novel carrier for genetic materials. The nanoparticles were obtained from poly(d,l-lactic acid) and poly(l-lysine)-graft-polysaccharide copolymers by using either a solvent evaporation method or a diafiltration method. The size of the particles prepared by the diafiltration method was controlled by varying the initial concentration of the graft copolymer. Nanoparticles as small as 60 nm in diameter were successfully obtained from the graft copolymers with high polysaccharide contents but not from the poly(l-lysine) homopolymer. Polysaccharide moieties on the surface of the nanoparticles were found to interact specifically with a particular lectin as verified by the aggregation assay. The polynucleotide adsorption capacity of the nanoparticles was increased with increasing polysaccharide contents in the graft copolymers, suggesting that the adsorption conformation of poly(l-lysine) moiety in the graft copolymer on the nanoparticle surface is different from that in poly(l-lysine) homopolymer. Moreover, the nanoparticles from the graft copolymer exhibited resistance against self-aggregation and nonspecific adsorption of serum proteins, presumably due to the polymer brush effect and/or exclusion effect from the polysaccharide graft chains. These results suggest that the nanoparticles prepared from poly(l-lysine)-graft-polysaccharide copolymer and poly(d,l-lactic acid) can serve as a good DNA carrier in vivo.