A versatile family of degradable non-viral gene carriers based on hyperbranched poly(ester amine)s

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Zhong, Zhiyuan and Song, Yan and Engbersen, Johan F.J. and Lok, Martin C. and Hennink, Wim E. and Feijen, Jan (2005) A versatile family of degradable non-viral gene carriers based on hyperbranched poly(ester amine)s. Journal of Controlled Release, 109 (1-3). pp. 317-329. ISSN 0168-3659

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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 °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 (not, vert, similar94–135 nm) and positively charged complexes. Polymer/DNA complexes (‘polyplexes’) based on these three polymers, and larger complexes of p(BDDA-AEP) (not, vert, similar497 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.
Item Type:Article
Additional information:Proceedings of the Twelfth International Symposium on Recent Advances in Drug Delivery Systems
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Science and Technology (TNW)
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Link to this item:http://purl.utwente.nl/publications/71342
Official URL:http://dx.doi.org/10.1016/j.jconrel.2005.06.022
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