Novel Biocompatible Cationic Copolymers Based on Polyaspartylhydrazide Being Potent as Gene Vector on Tumor Cells
Introduction. The reaction between !,"-poly(aspartylhydrazide) (PAHy), a water soluble synthetic polymer and 3-(carboxypropyl)trimethyl-ammonium chloride (CPTACl) produced copolymers bearing permanent positive charges (PAHy–CPTA) with molecular weight of 10 kDa and PAHy–CPTA copolymers differing in positive charge amount (18–58%) were chosen for biological investigations. Materials and methods. Biophysical properties of DNA/PAHy–CPTA polyplexes were evaluated in terms of DNA condensation, zeta potential and size distribution. Cytotoxicity studies on Neuro2A murine neuroblastoma cells evidenced absence of toxicity of these copolymers up to 300 2g/ml unlike linear polyethylenimine (LPEI) that…
Reversibly stable thiopolyplexes for intracellular delivery of genes.
Novel polyaspartamide non-viral carriers for gene therapy were synthesized by introducing, on the same polymer backbone, positively charged groups, for electrostatic interactions with DNA, and thiol groups for the formation of disulfide bridges between polymer chains. The introduction of thiols was aimed to have a vector with low redox potential sensitivity: disulfide crosslinking in fact, being stable in extracellular environment, allowed either to have stable complexes in plasma, that can protect DNA from metabolism, or to be reduced inside the cell, where the excess of glutathion in reduced form maintains a low redox potential. The consequent destabilization of the complex after disulfid…
Polyhydroxyethylaspartamide-spermine copolymers: Efficient vectors for gene delivery
Abstract Aim of this paper was that to prepare biocompatible, polyaspartamide based copolymers containing spermine or 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 exploiting the reactive hydroxyl groups in the polymeric side chains by subsequent activation reactions to obtain PHEA-Spermine (PHEA-Spm) and PHEA-Spermine-Butyramide (PHEA-Spm-C4). Molecular, physico-chemical and biological characterization of copolymers and interpolyelectrolyte complexes with plasmid DNA was performed. Experimental results evidenced that these copolymers are able…