Cationic graft copolymers as carriers for delivery of antisense-oligonucleotides

Self-assembling systems based on ionic complexes of DNA fragments (36 base pairs), bcl-2 antisense oligonucleotides (octadecamer), oligophosphates (25 phosphate groups) or acrylic oligomers (18 groups of phosphonic acid) with poly(L-lysine) (PLL) ((M) over bar (w)=130000 and 88 000) grafted with short poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) chains ((M) over bar (n)=4300 or 8 600) were studied by static and dynamic light scattering methods as systems suitable for gene therapy applications. The graft copolymers (GPLLs) with shorter PHPMA grafts ((M) over bar (n)=4300) provide polyelectrolyte complexes (PECs) with smaller (M) over bar (w) and R-H than the corresponding GPLLs with longer grafts ((M) over bar (n)=8600) and the same content of PLL. The lowest aggregation number of 2 was observed for PECs prepared from the GPLL with short grafts and 40 wt.-% of PLL. The complexes of oligonucleotides and DNA fragments with GPLLs showed quite similar behavior to that with oligophosphates and acrylic oligomer. The complexes prepared from GPLLs containing 40 wt.-% of PLL and at excess of oligophosphate were stable for at least 48 h under physiological conditions (0.15 m NaCl) and in bovine serum albumin's solutions (1 mg.mL(-1)). Additionally, polyanion exchange, reactions of the PECs in contact with poly(styrenesulfonate) and DNA were studied in 0.15 M NaCl solutions. The oligophosphates in complexes were at least partially substituted with high-molecular-weight polyanions. The structure of the initial PECs dominated the PEC structure after the exchange reaction.