Microwave-Assisted Synthesis of PHEA–Oligoamine Copolymers as Potential Gene Delivery Systems

Abstract

To prepare new copolymers, useful for gene delivery, based on alpha, beta-poly-(N-2-hydroxyethyl)-D, L-aspartamide (PHEA) as a polymeric backbone and bearing an oligoamine such as diethylenetriamine in the side chain. Moreover, in order to reduce solvent volume and make the reaction faster, microwave-assisted heating was used. PHEA copolymers bearing different amounts of diethylenetriamine were prepared using bis(4-nitrophenyl) carbonate as a condensing agent with the use of microwaves. Chemical, physico-chemical and biological characterization of PHEA-diethylenetriamine copolymers and their complexes obtained with DNA were performed. Copolymers showed good DNA complexing and condensing abilities depending on the oligoamine derivatization degree and good hemocompatibility. Moreover, plasmid DNA/copolymer polyplexes showed very good cytocompatibility on B16F10 and N2A cell lines. Results support the use of these copolymers as gene delivery systems in the future. Finally, the use of microwaves makes the proposed synthetic method advantageous as time and solvents are saved.