New pegylated polyaspartamide-based polyplexes as gene delivery vectors.

ABSTRACT

AIMS: To synthesize novel polyhydroxyethylaspartamide (PHEA) copolymers containing spermine (Spm) and polyethylene glycol (PEG) moieties in high yields, with the expectation that this material would show stealth properties and the ability to complex DNA by electrostatic interactions. MATERIALS & METHODS: PHEA-PEG-Spm copolymer was prepared with a two-step reaction. Chemical, physicochemical and biological characterizations of PHEA-PEG-Spm copolymers and their obtained polyplexes with pDNA were performed. RESULTS: The introduction of spermine in PHEA structure allows to obtain a copolymer bearing in the side chains polyamine moieties capable to interact with DNA. On the other hand, the introduction of PEG in polymeric structure increased the DNA condensing ability of PHEA-PEG-Spm copolymer in comparison with the derivatives without PEG (PHEA-Spm), and improved its characteristics of biocompatibility. CONCLUSIONS: PHEA-PEG-Spm copolymer shows excellent ability to complex and condense plasmidic DNA giving interpolyelectrolyte complexes to act as gene delivery systems. Moreover, PEGylation confers to the obtained interpolyelectrolyte complexes stealth properties.