title: Design of starch-graft-PEI polymers: an effective and biodegradable gene delivery platform.
abstract: Starch and starch derivatives are widely utilized pharmaceutical excipients. The concept of this study was to make use of starch as a biodegradable backbone and to modify it with low-toxic, but poor transfecting low molecular weight polyethylenimine (PEI) in order to achieve better transfection efficacy while maintaining enzymatic degradability. A sufficiently controllable conjugation could be achieved via a water-soluble intermediate of oxidized starch and an optimized reaction protocol. Systematic variation of MW fraction of the starch backbone and the amount of cationic side chains (0.8 kDa bPEI) yielded a series of starch-graft-PEI copolymers. Following purification and chemical characterization, nanoscale complexes with plasmid DNA were generated and studied regarding cytotoxicity and transfection efficacy. The optimal starch-graft-PEI polymers consisted of >100 kDa MW starch and contained 30% (wt) of PEI, showing similar transfection levels as 25 kDa bPEI, and being less cytotoxic and enzymatically biodegradable.
authors.affiliation: Department of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Center for Infection Research (HZI), Saarland University , D-66123 Saarbrücken, Germany.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Yamada
authors.forename: Brigitta
authors.initials: B
authors.lastname: Loretz
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry / Q000633:toxicity; D010316:Particle Size; D010957:Plasmids / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry* / Q000633:toxicity; D012995:Solubility; D013213:Starch / Q000737:chemistry* / Q000633:toxicity; D013499:Surface Properties; D014162:Transfection / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D011094:Polyethyleneimine; D013213:Starch; D004247:DNA