title: A versatile family of degradable non-viral gene carriers based on hyperbranched poly(ester amine)s.
abstract: A variety of degradable hyperbranched poly(ester amine)s containing primary, secondary and tertiary amino groups, were synthesized and evaluated as non-viral gene carriers. The polymers were obtained in high yields through a Michael-type conjugate addition of diacrylate monomers with trifunctional amine monomers. Analysis of degradation products using liquid chromatography-mass spectroscopy (LC-MS) demonstrated that all poly(ester amine)s had a hyperbranched structure with a degree of branching of approximately 0.30. These poly(ester amine)s were readily water-soluble and degradable under physiological conditions (pH 7.4, 37 degrees C), in which more than 10% ester bonds were hydrolyzed within 4 h. Moreover, these hyperbranched poly(ester amine)s showed high buffering capacities between pH 5.1 and 7.4. Three out of nine synthesized polymers, i.e. p(HDDA-AEP), p(HDDA-AMP), and p(BDDA-AMP), were shown to effectively condense plasmid DNA into small-sized (approximately 94-135 nm) and positively charged complexes. Polymer/DNA complexes ('polyplexes') based on these three polymers, and larger complexes of p(BDDA-AEP) (approximately 497 nm) were able to transfect COS-7 cells in vitro. Importantly, the transfection activity of polyplexes was preserved in the presence of serum proteins. The highest transfection level was observed for p(HDDA-AEP) polyplex which had a transfection efficiency higher than or comparable to that polyplexes of polyethylenimine (PEI) and poly(2-(dimethylamino)ethyl methacrylate) (pDMAEMA). Furthermore, these poly(ester amine)s revealed no or low cytotoxicity. These results demonstrated that hyperbranched poly(ester amine)s can be applied as safe and efficient gene delivery polymers.
authors.affiliation: Department of Polymer Chemistry and Biomaterials, Institute for Biomedical Technology (BMTI), Faculty of Science and Technology, University of Twente, Enschede, The Netherlands.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhong
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.forename: Johan F J
authors.initials: JF
authors.lastname: Engbersen
authors.forename: Martin C
authors.initials: MC
authors.lastname: Lok
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.forename: Jan
authors.initials: J
authors.lastname: Feijen
mesh_terms: D000465:Algorithms; D000818:Animals; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers; D004563:Electrochemistry; D015316:Genetic Therapy / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D010316:Particle Size; D010957:Plasmids / Q000235:genetics; D011091:Polyesters / Q000737:chemistry*; D014162:Transfection
chemical_list: D004337:Drug Carriers; D011091:Polyesters; D004247:DNA