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A combinatorial library of triazine-cored polymeric vectors for pDNA delivery in vitro and in vivo

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Abstract

A set of triazine-cored cationic amphiphilic polymers (TAPs) composed of low molecular weight (Mw) polyethylenimine (LPEI, B) and amphiphilic Jeffamine (A) were prepared with controllable composition and molecular size, and further characterized for plasmid DNA (pDNA) delivery both in vitro and in vivo. These new polymers condensed pDNA efficiently at a polymer/pDNA weight ratio of 5 with particle sizes below 200 nm. The introduction of Jeffamine in the polymers significantly improved the cellular uptake of pDNA, but without increasing its toxicity compared with the parent LPEI. The best formulation resulted in 6- and 29-fold transfection efficiencies of PEI 25k in vitro and in vivo in mdx mice, respectively. Higher transfection efficiency was achieved with more lipophilic A1/A3-based polymers in vitro, with 1A11B3 and 1A12B3 showing the greatest delivery performance. However, the lipophilicity of the TAPs is less critical in vivo as the less lipophilic A2/A4 constructed TAPs also performed similarly well as the more lipophilic A1/A3 constructed ones. In addition, a synergistic effect of LPEI and Jeffamine via chemical conjugation for the delivery of pDNA was revealed in transfection efficiency. These results indicate that the appropriate positive surface and particle size of polymer/pDNA complex and the composition and hydrophilic–lipophilic balance (HLB) of polymers are crucial for effective delivery, although intricate matching exists between A and B in the TAP composition. Triazine-cored cationic amphiphilic polymers are safe and potentially effective carriers for gene/drug delivery.

Graphical abstract: A combinatorial library of triazine-cored polymeric vectors for pDNA delivery in vitro and in vivo

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Publication details

The article was received on 20 Dec 2016, accepted on 19 Apr 2017 and first published on 20 Apr 2017


Article type: Paper
DOI: 10.1039/C6TB03311C
Citation: J. Mater. Chem. B, 2017, Advance Article
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    A combinatorial library of triazine-cored polymeric vectors for pDNA delivery in vitro and in vivo

    M. Wang, B. Wu, J. D. Tucker, P. Lu and Q. Lu, J. Mater. Chem. B, 2017, Advance Article , DOI: 10.1039/C6TB03311C

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