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A Combinatorial Library of Triazine-cored Polymeric Vectors for pDNA delivery in vitro and in vivo

Abstract

A series of triazine-cored cationic amphiphlic polymers (TAPs) composed of low molecular weight (Mw) polyethylenimine (LPEI, B) and amphiphilic Jeffamine (A) were controllable prepared in composition and molecular size, and furhter characterized for plasmid DNA (pDNA) delivery both in vitro and in vivo. These new polymers condensed pDNA efficiently at the weight ratio 5 of polymer/pDNA with particles size below 200 nm. The introduction of Jeffamine in the polymers significantly improved the cellular uptake of pDNA, but without increases in toxicity compared with the parent LPEI. The best formulation produced transfection efficiency 6 and 29-fold 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, lipophilicity of the TAPs is less critical in vivo as the lower lipophilicity A2/A4 constructed TAPs also performed similarly well as those with the higher 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 appropriate positive surface and particle size of polymer/pDNA complex and composition, hydrophilic-lipophilic-balance (HLB) within polymers are crucial for effective delivery system, although intricate matching exists between A and B in TAP composition. Triazine-cored cationic amphiphilic polymers are safe and potentially effective carriers for gene/drug delivery.

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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, Accepted Manuscript
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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, Accepted Manuscript , DOI: 10.1039/C6TB03311C

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