Polycationic Graft Copolymers as Carriers for Oligonucleotide Delivery. Complexes of Oligonucleotides with Polycationic Graft Copolymers

Abstract

Self-assembling systems based on ionic complexes of oligonucleotides (36 base pairs) and model oligophosphates (polymerization degree of 35) with high molecular poly( l -lysine) molecules ( M w = 134 000) grafted with short poly[ N -(2-hydroxypropyl)methacrylamide] chains ( M w = 7000) were studied as systems suitable for gene therapy applications. Poly( l -lysine) and poly(trimethylammonioethyl methacrylate chloride) homopolycations were used for comparison. The physicochemical properties of polyelectrolyte complexes (PEC) were examined by static and dynamic light scattering methods. While PECs prepared with homopolycations tend to aggregate, particularly at high degrees of charge conversions, the complexes prepared with graft copolymers are soluble at any charge conversions in aqueous solutions. The complexes prepared with an excess of oligophosphates were found to be stable in physiological salt conditions and in the bovine serum albumin solutions (1 mg/mL). A formation of PEC/albumin complexes and large aggregates was observed for uncompensated PECs with cationic excess.