Microwave-assisted synthesis of PHEA-oligoamine copolymers as potential gene delivery systems

Abstract

Aims - Copolymers bearing oligoamines and having buffering capacity in the endosomal pH range seems very promising as non viral vectors in gene delivery, due to the great importance of endosomal escaping for an efficient endocellular DNA release. Aim of this paper was to prepare new copolymers based on α,β-poly-(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) as polymeric backbone and bearing an oligoamine, such as diethylentriamine (DETA) in the side chain and useful for gene delivery. Moreover in order to reduce solvent volume and to make faster the reaction, microwave-assisted has been used. Materials and methods - PHEA copolymers bearing different amount of DETA were prepared by using bis(4-nitrophenyl)carbonate (4-NPBC), as condensant agent and involving microwaves. Chemical, physico-chemical and biological characterization of obtained PHEA-DETA copolymers and their complexes obtained with DNA were performed. Results - Copolymers showed great DNA complexing and condensing abilities depending on the oligoamine derivatization degree and good haemocompatibility. Moreover pDNA/copolymer polyplexes showed very good cytocompatibility on B16F10 and N2A cell lines. Conclusions - Obtained results support the use of these copolymers as gene delivery systems in the future. Finally the use of a microwaves make the proposed synthetic method advantageus because time and solvent saving.