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Poly(Amido Amine)s Containing Agmatine and Butanol Side Chains as Efficient Gene Carriers
Authors:Young‐Wook Won  Marc Ankoné  Johan F. J. Engbersen  Jan Feijen  Sung Wan Kim
Affiliation:1. Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, USA;2. Division of Cardiothoracic Surgery, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah, USA;3. Department of Biomedical Chemistry, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands
Abstract:A new type of bioreducible poly(amido amine) copolymer is synthesized by the Michael addition polymerization of cystamine bisacrylamide (CBA) with 4‐aminobutylguanidine (agmatine, AGM) and 4‐aminobutanol (ABOL). Since the positively charged guanidinium groups of AGM and the hydroxybutyl groups of ABOL in the side chains have shown to improve the overall transfection efficiency of poly(amido amine)s, it is hypothesized that poly(CBA‐ABOL/AGM) synthesized at the optimal ratio of both components would result in high transfection efficiency and minimal toxicity. In this study, a series of the poly(CBA‐ABOL/AGM) copolymers is synthesized as gene carriers. The polymers are characterized and luciferase transfection efficiencies of the polymers in various cell lines are investigated to select the ideal ratio between AGM and ABOL. The poly(CBA‐ABOL/AGM) containing 80% AGM and 20% ABOL has shown the best transfection efficiency with the lowest cytotoxicity, indicating that this polymer is very promising as a potent and nontoxic gene carrier.
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Keywords:biological applications of polymers  drug delivery systems  gene delivery  nanoparticles  structure‐property relations  transfection
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