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Hyperbranched poly(ethylenimine-co-oxazoline) by thiol–yne chemistry for non-viral gene delivery: investigating the role of polymer architecture

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Abstract

Cationic polymers have been widely employed as gene delivery vectors to help circumvent extracellular and intracellular delivery barriers. Among them, polyethylenimine (PEI) is the most commonly used despite its associated high cytotoxicity. PEI is typically obtained by uncontrolled ring opening polymerisation of aziridine, leading to either linear polymer architectures with only secondary amines, or branched architectures containing primary, secondary, and tertiary amines. In contrast, we describe the preparation of hyperbranched poly(ethylenimine-co-oxazoline) that contains only secondary amines, via a fast thiol–yne based one pot reaction. A small library of these compounds with varying PEI contents was then used to study the effect of polymer architecture on pDNA polyplex formation, cytotoxicity, and in vitro transfection studies with plasmid DNA. Hyperbranched poly(ethylenimine-co-oxazoline) was found to have reduced toxicity compared to the commercial standard 25 000 g mol−1 branched PEI (bPEI), with transfection efficiencies only slightly lower than its bPEI counterpart. Obtained results highlight the importance of the polymer architecture on the transfection efficiency of a gene delivery system, which was demonstrated by excluding other parameters such as molecular weight and charge density.

Graphical abstract: Hyperbranched poly(ethylenimine-co-oxazoline) by thiol–yne chemistry for non-viral gene delivery: investigating the role of polymer architecture

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Publication details

The article was received on 20 Nov 2018, accepted on 25 Jan 2019 and first published on 29 Jan 2019


Article type: Paper
DOI: 10.1039/C8PY01648H
Citation: Polym. Chem., 2019, Advance Article

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    Hyperbranched poly(ethylenimine-co-oxazoline) by thiol–yne chemistry for non-viral gene delivery: investigating the role of polymer architecture

    A. B. Cook, R. Peltier, J. Zhang, P. Gurnani, J. Tanaka, J. A. Burns, R. Dallmann, M. Hartlieb and S. Perrier, Polym. Chem., 2019, Advance Article , DOI: 10.1039/C8PY01648H

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