Polyhydroxyethylaspartamide-spermine copolymers: Efficient vectors for gene delivery

Aim of this paper was that to prepare biocompatible, polyaspartamide based copolymers containing spermineor spermine/hydrophobic side chains able to condense nucleic acids and to transfect mammalian cells.Copolymers were prepared starting from α,β-poly-(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) and exploitingthe reactive hydroxyl groups in the polymeric side chains by subsequent activation reactions to obtain PHEASpermine(PHEA-Spm) and PHEA-Spermine-Butyramide (PHEA-Spm-C4). Molecular, physico-chemical andbiological characterization of copolymers and interpolyelectrolyte complexes with plasmid DNAwas performed.Experimental results evidenced that these copolymers are able to form complexes with plasmid DNA already atlow polycation/DNAweight ratio ranging from 0.75/1 to 2/1. Interpolyelectrolyte complexes with decreased sizewere obtained when increasing the polycation/DNA weight ratio, until nanosized dimensions were reached.Copolymers aswell as complexeswere not haemolytic and non toxic in vitro. In vitro cell transfection with PHEAderivatives showed good biocompatibility and high transfection efficiency (luciferase) in cancer cells incomparison with commercially available, but toxic transfection agents.