In this study, the gene delivery properties of new hyperbranched poly(amido amine)s (PAAs) with disulfide linkages in the main chain were investigated in comparison with their linear analogs. Eight different bioreducible PAAs were prepared by Michael addition of N,N'-bisacryloylpiperazine (BP) with cystamine (CYST) or N,N'-dimethylcystamine (DMC) and of N,N'-cystaminebisacrylamide (CBA) with N,N'-ethylenediamine (EDA) or N,N'-dimethylethylenediamine (DMEDA). In order to study the effect of terminal groups on the transfection efficiency, each polymer was terminated with 4-aminobutanol (ABOL) or with 2-aminoethanol (ETA). The hyperbranched and the linear PAAs generally formed polyplexes with plasmid DNA with sizes around 200 nm and positive zeta potentials ranging from + 10 to + 22 mV at polymer/DNA weight ratios equal or higher than 3/1. Remarkably low or no cytotoxicity was observed for both hyperbranched and linear PAAs. Hyperbranched CBA-containing PAAs showed higher gene expression in DNA transfection tests with COS-7 cells than their linear analogs and up to two times higher than linear PEI that was used as the reference polymer. Transfection efficiencies of the branched PAAs were generally enhanced by the presence of serum, which is a promising property for future in vivo studies with these hyperbranched PAAs.
Effects of branched or linear architecture of bioreducible poly(amido amine)s on their in vitro gene delivery properties / F. Martello, M. Piest, J.F.J. Engbersen, P. Ferruti. - In: JOURNAL OF CONTROLLED RELEASE. - ISSN 0168-3659. - 164:3(2012 Dec 28), pp. 372-379. ((Intervento presentato al 12. convegno European Symposium on Controlled Drug Delivery tenutosi a Egmond aan Zee nel 2012.
|Titolo:||Effects of branched or linear architecture of bioreducible poly(amido amine)s on their in vitro gene delivery properties|
MARTELLO, FEDERICO (Primo)
FERRUTI, PAOLO (Ultimo)
|Parole Chiave:||Disulfide reduction; Gene delivery; Hyperbranched poly(amido amine); Michael addition; Polyplex|
|Settore Scientifico Disciplinare:||Settore CHIM/04 - Chimica Industriale|
Settore CHIM/09 - Farmaceutico Tecnologico Applicativo
|Data di pubblicazione:||28-dic-2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.jconrel.2012.07.029|
|Appare nelle tipologie:||01 - Articolo su periodico|