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Polymers 2018, 10(4), 442; https://doi.org/10.3390/polym10040442

Comparative Study of Diethylaminoethyl-Chitosan and Methylglycol-Chitosan as Potential Non-Viral Vectors for Gene Therapy

1
Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoi pr. VO 31, St. Petersburg 199004, Russia
2
Institute of Chemistry, St. Petersburg State University, Universitetskii pr. 26, Petrodvorets, St. Petersburg 198504, Russia
3
University of Vienna, Althanstrasse, 14, A-1090 Vienna, Austria
4
Department of Biomolecular Sciences, School of Pharmacy, University of Urbino, 61029 Urbino, Italy
5
Department of Pharmacology & Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China
6
Department of Chemical Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK
7
Research Institute of Influenza, ul. Prof. Popova 15/17, St. Petersburg 197376, Russia
8
Peter the Great St. Petersburg Polytechnic University, Polytechnicheskaya ul. 29, St. Petersburg 195251, Russia
9
Institute of Experimental Medicine, Almazov National Medical Research Centre, ul. Akkuratova 2, St. Petersburg 197341, Russia
*
Author to whom correspondence should be addressed.
Received: 5 March 2018 / Revised: 11 April 2018 / Accepted: 11 April 2018 / Published: 14 April 2018
(This article belongs to the Special Issue Interpolymer Complexes)
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Abstract

In this paper, we compared the transfection efficiency and cytotoxicity of methylglycol-chitosan (MG-CS) and diethylaminoethyl-chitosan (DEAE-CSI and DEAE-CSII with degrees of substitution of 1.2 and 0.57, respectively) to that of Lipofectamine (used as a reference transfection vector). MG-CS contains quaternary amines to improve DNA binding, whereas the DEAE-CS exhibits pH buffering capability that would ostensibly enhance transfection efficiency by promoting endosomal escape. Gel retardation assays showed that both DEAE-CS and MG-CS bound to DNA at a polysaccharide:DNA mass ratio of 2:1. In Calu-3 cells, the DNA transfection activity was significantly better with MG-CS than with DEAE-CS, and the efficiency improved with increasing polysaccharide:DNA ratios. By contrast, the efficiency of DEAE-CSI and DEAE-CSII was independent of the polysaccharide:DNA ratio. Conversely, in the transfection-recalcitrant JAWSII cells, both Lipofectamine and MG-CS showed significantly lower DNA transfection activity than in Calu-3 cells, whereas the efficiency of DEAE-CSI and DEAE-CSII was similar in both cell lines. The toxicity of DEAE-CS increased with increasing concentrations of the polymer and its degree of substitution, whereas MG-CS demonstrated negligible cytotoxicity, even at the highest concentration studied. Overall, MG-CS proved to be a more efficient and less toxic transfection agent when compared to DEAE-CS. View Full-Text
Keywords: diethylaminoethyl-chitosan; methylglycol-chitosan; polyplex; cell transfection; gene delivery diethylaminoethyl-chitosan; methylglycol-chitosan; polyplex; cell transfection; gene delivery
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Raik, S.V.; Andranovitš, S.; Petrova, V.A.; Xu, Y.; Lam, J.K.-W.; Morris, G.A.; Brodskaia, A.V.; Casettari, L.; Kritchenkov, A.S.; Skorik, Y.A. Comparative Study of Diethylaminoethyl-Chitosan and Methylglycol-Chitosan as Potential Non-Viral Vectors for Gene Therapy. Polymers 2018, 10, 442.

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