title: A library of strictly linear poly(ethylene glycol)-poly(ethylene imine) diblock copolymers to perform structure-function relationship of non-viral gene carriers.
abstract: A library of 39 strictly linear poly(ethylene glycol)-poly(ethylene imine) (PEG-PEI) diblock copolymers was synthesized for the delivery of plasmid DNA using PEG of 2, 5, or 10 kDa in combination with linear PEI with a molecular weight (MW) ranging from 1.5 to 10.8 kDa. In contrast to other approaches, the copolymers demonstrated a clear separation between the hydrophilic PEG and the nucleic acid condensing PEI moieties. Hence, the hypothesis was that PEG may not sterically counteract the interaction between the nucleic acid and PEI and that consequently, the copolymers are perfectly suited to build small and stable polyplexes. Analysis of the polyplexes revealed structure-function relationships and the general guideline was that the PEG domain had a greater influence on the physicochemical properties of the polyplexes than PEI. A PEG content higher than 50% led to small (<150 nm), nearly neutral polyplexes with favorable stability. The transfection efficacy of these polyplexes was significantly reduced compared to the PEI homopolymer, but was restored by the application of the corresponding degradable copolymer, which involved a redox triggerable PEG domain. In conclusion, valuable design criteria for the optimization of gene delivery carriers, which is only possible through the screening of such a large library, were gained.
authors: University of Regensburg, Department of Pharmaceutical Technology, 93053 Regensburg, Germany. miriam.breunig@chemie.uni-regensburg.de
authors: Sonja
authors: S
authors: Bauhuber
authors: Renate
authors: R
authors: Liebl
authors: Luise
authors: L
authors: Tomasetti
authors: Reinhard
authors: R
authors: Rachel
authors: Achim
authors: A
authors: Goepferich
authors: Miriam
authors: M
authors: Breunig
mesh_terms: D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D010957:Plasmids / Q000235:genetics; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014162:Transfection / Q000379:methods*
chemical_list: C544016:poly(ethylene glycol)-co-poly(ethyleneimine); D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA