A versatile family of degradable non-viral gene carriers based on hyperbranched poly(ester amine)s.
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.
Zhong
Zhiyuan
Z
Department of Polymer Chemistry and Biomaterials, Institute for Biomedical Technology (BMTI), Faculty of Science and Technology, University of Twente, Enschede, The Netherlands.
Song
Yan
Y
Engbersen
Johan F J
JF
Lok
Martin C
MC
Hennink
Wim E
WE
Feijen
Jan
J
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
D004337:Drug Carriers; D011091:Polyesters; D004247:DNA