title: Effects of charge density and hydrophobicity of poly(amido amine)s for non-viral gene delivery.
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.
authors.affiliation: Department of Biomedical Chemistry, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Piest
authors.affiliation: Department of Biomedical Chemistry, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands. Electronic address: j.f.j.engbersen@utwente.nl.
authors.forename: Johan F J
authors.initials: JFJ
authors.lastname: Engbersen
mesh_terms: D000107:Acetylation; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry; D005453:Fluorescence; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D011073:Polyamines / Q000737:chemistry* / Q000494:pharmacology; D014162:Transfection
chemical_list: C531249:Poly(amidoamine); D011073:Polyamines; D004247:DNA