title: A comparison of thiolated and disulfide-crosslinked polyethylenimine for nonviral gene delivery.
abstract: Branched polyethylenimine (25 kDa) is thiolated and compared with redox-sensitive crosslinked derivatives. Both polymers thiol contents are assessed; the thiolated polymers have 390-2300 mmol SH groups/mol, whereas the crosslinked polymers have lower thiol contents. Cytotoxicity assays show that both modified polymers give lower hemolysis than unmodified PEI. Increased thiol content increases gene transfer efficiency but also elevates cytotoxicity. Crosslinking improves plasmid DNA condensation and enhances transfection efficiency, but extensive crosslinking overstabilizes the polyplexes and decreases transfection, emphasizing the need to balance polyplex stabilization and unpacking. Thus, at low levels of crosslinking, 25 kDa PEI can be an efficient redox-sensitive carrier system.
authors.affiliation: Reading School of Pharmacy, University of Reading, Whiteknights, PO Box 224, RG6 6AD, Reading, United Kingdom.
authors.forename: Latha
authors.initials: L
authors.lastname: Aravindan
authors.forename: Katrina A
authors.initials: KA
authors.lastname: Bicknell
authors.forename: Gavin
authors.initials: G
authors.lastname: Brooks
authors.forename: Vitaliy V
authors.initials: VV
authors.lastname: Khutoryanskiy
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Williams
mesh_terms: D002021:Buffers; D016923:Cell Death; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004220:Disulfides / Q000138:chemical synthesis / Q000737:chemistry*; D005453:Fluorescence; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006461:Hemolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D008422:Materials Testing; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry*; D055672:Static Electricity; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D014162:Transfection; D014780:Viruses / Q000378:metabolism
chemical_list: D002021:Buffers; D003432:Cross-Linking Reagents; D004220:Disulfides; D013438:Sulfhydryl Compounds; D011094:Polyethyleneimine
keywords: crosslinking; gene delivery; polyamines; polyethylene imine; polyplexes