A library of strictly linear poly(ethylene glycol)-poly(ethylene imine) diblock copolymers to perform structure-function relationship of non-viral gene carriers

Bauhuber, Sonja and Liebl, Renate and Tomasetti, Luise and Rachel, Reinhard and Goepferich, Achim and Breunig, Miriam (2012) A library of strictly linear poly(ethylene glycol)-poly(ethylene imine) diblock copolymers to perform structure-function relationship of non-viral gene carriers. JOURNAL OF CONTROLLED RELEASE, 162 (2). pp. 446-455. ISSN 0168-3659,

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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. (C) 2012 Elsevier B. V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: DNA/TRANSFERRIN-PEI COMPLEXES; MOLECULAR-WEIGHT; IN-VIVO; GLYCOL)-BLOCK-POLYETHYLENIMINE COPOLYMERS; EXTENDED CIRCULATION; GLYCOL) COPOLYMERS; BLOCK-COPOLYMERS; DNA CONDENSATION; DELIVERY-SYSTEMS; NUCLEIC-ACIDS; Polyplexes; Poly(ethylene imine); PEGylation; Linear diblock copolymer; Degradation; Stability
Subjects: 500 Science > 530 Physics
600 Technology > 615 Pharmacy
Divisions: Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 06 May 2020 06:27
Last Modified: 06 May 2020 06:27
URI: https://pred.uni-regensburg.de/id/eprint/18119

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