Polycationic graft copolymers as carriers for oligonucleotide delivery. Complexes of oligonucleotides with polycationic graft copolymers

Self-assembling systems based on ionic complexes of oligonucleotides (36 ba se 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)methacryIamide] chains (M-w = 7000) were studied as sys tems suitable for gene therapy applications. Poly(L-l ysine) and poly(trime thylammonioethyl methacrylate chloride) homopolycations were used for compa rison. The physicochemical properties of polyelectrolyte complexes (PEC wer e examined by static and dynamic light scattering methods. While PECs prepa red with homopolycations tend to aggregate, particularly at high degrees of charge conversions, the complexes prepared with graft copolymers are solub le at any charge conversions in aqueous solutions. The complexes prepared w ith an excess of oligophosphates were found to be stable in physiological s alt conditions and in the bovine serum albumin solutions (1 mg/mL). A forma tion of PEC/albumin complexes and large aggregates was observed for uncompe nsated PECs with cationic excess.