DNA complexes with block and graft copolymers of N-(2-hydroxypropyl) methacrylamide and 2-(trimethylammonio)ethyl methacrylate

Block and graft copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) with 2- (trimethylammonio)ethyl methacrylate (TMAEM) were synthesized for the p reparation of polyelectrolyte complexes with calf thymus DNA intended for t argeted delivery of genes in vivo. In this study, the effects of the poly(H PMA) content of copolymers on the parameters of the interpolyelectrolyte co mplexes is investigated. Static and dynamic light scattering methods were u sed as a main tool for characterization. The ability of the copolymers to c ondense DNA was studied by the ethidium bromide displacement method. The st ability of the complexes against precipitation in 0.15 M NaCl and the resis tance of the complexed DNA to the action of nucleases was also studied. It was found that the presence of poly(HPMA) in the copolymers has not signifi cantly affected the ability of poly(TMAEM) parts of the copolymers to form complexes with DNA, but has an effect on molecular parameters and aggregati on (precipitation) of the complexes. The size of the complexes increases wi th increasing poly(HPMA) content while their apparent molecular weight decr eases. The complex stability against precipitation in 0.15 M NaCl strongly depends on the amount of poly(HPMA) in the copolymer structure. The presenc e of a sufficiently high content of poly(HPMA) is a prerequisite for achiev ing good stability. The structure of the complexes changes with increasing poly(HPMA) content from 'soft balls' to the polymer coil. The density of th e complexes decreases with increasing poly(HPMA) content independently of t he copolymer structure. The DNA complexes of all copolymers showed very goo d nuclease stability.