Effects of charge density and hydrophobicity of poly(amido amine)s for non-viral gene delivery

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Abstract

High cationic charge densities in polymeric vectors result in tight DNA condensation, leading to small highly positively charged polyplexes which show generally high cellular uptake in vitro. However, high cationic charge densities also introduce membrane-disruptive properties to the polymers, thereby frequently causing high cytotoxities. We previously developed poly(amido amine)s with repetitive disulfide linkages in the main chain (SS-PAAs) that are significantly less toxic than PEI, due to fast intracellular degradation of these polymers by bioreductive cleavage of the disulfide bonds. In this study we have investigated the effects of variation in charge density and hydrophobicity on the gene delivery properties of these polymers by varying the degree of acetylation and benzoylation in SS-PAAs with aminobutyl side chains. It was found that introduction of hydrophobic benzoyl groups results in higher transfection efficiencies, both in the absence and presence of serum.
Original languageEnglish
Pages (from-to)83-90
JournalJournal of controlled release
Volume148
Issue number1 (special issue)
DOIs
Publication statusPublished - 2010
Event11th European Symposium on Controlled Drug Delivery, ESCDD 2010 - Hotel Zuiderduin, Egmond aan Zee (NL), Netherlands
Duration: 7 Apr 20109 Apr 2010
Conference number: 11

Keywords

  • Polyplex
  • Poly(amido amine)
  • Disulfide reduction
  • Michael addition
  • Gene delivery

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