title: Effects of branched or linear architecture of bioreducible poly(amido amine)s on their in vitro gene delivery properties.
abstract: 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 200nm and positive zeta potentials ranging from +10 to +22mV 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. In this study the ease of synthetic modification of both linear and hyperbranched poly(amido amide)s and the versatility of hyperbranched PAAs in regulating DNA transfection and cytotoxicity are demonstrated. The results show the large possibilities for this class of polymers to provide polymeric vectors with controllable properties for gene therapy applications.
authors: Dipartimento di Chimica Organica e Industriale, Universitá degli Studi di Milano, via Venezian 21, 20133 Milan, Italy.
authors: Federico
authors: F
authors: Martello
authors: Martin
authors: M
authors: Piest
authors: Johan F J
authors: JF
authors: Engbersen
authors: Paolo
authors: P
authors: Ferruti
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004220:Disulfides / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D018014:Gene Transfer Techniques; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D010316:Particle Size; D011073:Polyamines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D004220:Disulfides; D004337:Drug Carriers; C531249:Poly(amidoamine); D011073:Polyamines; D004247:DNA