6533b82dfe1ef96bd129151c

RESEARCH PRODUCT

Polyhydroxyethylaspartamide-spermine copolymers: Efficient vectors for gene delivery

Gaetano GiammonaSergio ScireGennara CavallaroMariano LicciardiManfred OgrisErnst Wagner

subject

Biocompatibilitygene delivery polyaspartamideCell SurvivalStereochemistryPharmaceutical ScienceSpermineGene deliveryBiologyTransfectionpolycationDNA Adductschemistry.chemical_compoundCell Line TumorCopolymerHumansLuciferasesCells CulturedErythrocyte MembraneGenetic transferinterpolyelectrolyte complexesGene Transfer TechniquesDNATransfectionCombinatorial chemistrychemistryNucleic acidSperminePeptidesDNA

description

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 to form complexes with plasmid DNA already at low polycation/DNA weight ratio ranging from 0.75/1 to 2/1. Interpolyelectrolyte complexes with decreased size were obtained when increasing the polycation/DNA weight ratio, until nanosized dimensions were reached. Copolymers as well as complexes were not haemolytic and non toxic in vitro. In vitro cell transfection with PHEA derivatives showed good biocompatibility and high transfection efficiency (luciferase) in cancer cells in comparison with commercially available, but toxic transfection agents.

yearjournalcountryeditionlanguage
2008-03-28Journal of Controlled Release
https://doi.org/10.1016/j.jconrel.2008.07.001