Novel poly(amidoamine)s with pendant primary amines as highly efficient gene delivery vectors

Three poly(amidoamine)s with pendant primary amines were synthesized by Michael polyaddition of a diamine to N,N-methylenebis(acrylamide). The poly(amidoamine)s with primary and tertiary amines possess a high buffer capacity between pH = 5 and 7, which facilitates the escape of polymer/DNA complexes from endosomes according to the 'proton sponge hypothesis'. In vitro cytotoxicity of poly(amidoamine)s depends on the side-chain structure of the polymer. Polymers 1a-1c can condense plasmid DNA by electrostatic interactions to form nanosized polyelectrolyte complexes with a positive surface charge. In vitro transfection results indicate that the transfection efficiency of polymer 1b under optimized conditions is comparable to that of commercial branched PEI 25,000.