title: Poly(ethylenimine) conjugated bioreducible dendrimer for efficient gene delivery.
abstract: Branched poly(ethylenimine) (PEI) 25 kDa is an efficient gene delivery vector with outstanding gene condensation ability and great endosome escape activity. However, it also induces higher cytotoxicity. Transfection efficiency and toxicity of PEI are highly dependent upon their molecular weight and structure. We developed a bioreducible poly(ethylenimine) (PEI (-s-s-)) derived from low molecular weight PEI (1.8 kDa) for efficient gene delivery. Bioreducible core molecule is expected to increase molecular weight and reduce the cytotoxicity of the copolymer. PEI (-s-s-) polyplexes showed higher transfection efficiency and lower cytotoxicity compared to branched PEI 25 kDa, Lipofectamine® 2000 and, FuGENE® 6. In addition, PEI (-s-s-) derivative (16 kDa) formed stable polyplexes with a zeta-potential value of +34 mV and polyplex size of 61 nm. PEI (-s-s-) derivative (16 kDa) showed excellent transfection efficiency: 3.6 times higher than branched PEI 25 kDa in HeLa cells and 7.4 times higher than Lipofectamine® 2000 in H9C2 cell. The derivatives also showed lower cytotoxicity compared with Lipofectamine® 2000 and PEI 25 kDa in various cell types. In addition, newly synthesized PEI (-s-s-) derivatives have high reproducibility.
authors.affiliation: Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Kihoon
authors.initials: K
authors.lastname: Nam
authors.affiliation: Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Simhyun
authors.initials: S
authors.lastname: Jung
authors.affiliation: Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Joung-Pyo
authors.initials: JP
authors.lastname: Nam
authors.affiliation: Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: SW.Kim@pharm.utah.edu.
authors.forename: Sung Wan
authors.initials: SW
authors.lastname: Kim
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D050091:Dendrimers / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D015394:Molecular Structure; D008970:Molecular Weight; D011094:Polyethyleneimine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D014162:Transfection / Q000379:methods*
chemical_list: D050091:Dendrimers; C411955:FuGene; D008055:Lipids; C086724:Lipofectamine; D049452:Green Fluorescent Proteins; D011094:Polyethyleneimine; D004247:DNA; D008156:Luciferases
keywords: Biodegradation; Cytotoxicity; Dendrimer; Gene expression; Poly(ethylenimine)