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Open AccessArticle

Effect of Double Substitution in Cationic Chitosan Derivatives on DNA Transfection Efficiency

1
Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoi pr. VO 31, 199004 St. Petersburg, Russia
2
Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, Finland
3
Institute of Experimental Medicine, Akademika Pavlova st. 12, 197376 St. Petersburg, Russia
*
Author to whom correspondence should be addressed.
Polymers 2020, 12(5), 1057; https://doi.org/10.3390/polym12051057
Received: 19 April 2020 / Revised: 2 May 2020 / Accepted: 3 May 2020 / Published: 5 May 2020
(This article belongs to the Special Issue Biomedical Polymer Materials II)
Recently, much effort has been expended on the development of non-viral gene delivery systems based on polyplexes of nucleic acids with various cationic polymers. Natural polysaccharide derivatives are promising carriers due to their low toxicity. In this work, chitosan was chemically modified by a reaction with 4-formyl-n,n,n-trimethylanilinium iodide and pyridoxal hydrochloride and subsequent reduction of the imine bond with NaBH4. This reaction yielded three novel derivatives, n-[4-(n’,n’,n’-trimethylammonium)benzyl]chitosan chloride (TMAB-CS), n-[(3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridine)methyl]chitosan chloride (Pyr-CS), and n-[4-(n’,n’,n’’-trimethylammonium)benzyl]-n-[(3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridine)methyl]chitosan chloride (PyrTMAB-CS). Their structures and degrees of substitution were established by 1H NMR spectroscopy as DS1 = 0.22 for TMAB-CS, DS2 = 0.28 for Pyr-CS, and DS1 = 0.21, DS2 = 0.22 for PyrTMAB-CS. Dynamic light scattering measurements revealed that the new polymers formed stable polyplexes with plasmid DNA encoding the green fluorescent protein (pEGFP-N3) and that the particles had the smallest size (110–165 nm) when the polymer:DNA mass ratio was higher than 5:1. Transfection experiments carried out in the HEK293 cell line using the polymer:DNA polyplexes demonstrated that Pyr-CS was a rather poor transfection agent at polymer:DNA mass ratios less than 10:1, but it was still more effective than the TMAB-CS and PyrTMAB-CS derivatives that contained a quaternary ammonium group. By contrast, TMAB-CS and PyrTMAB-CS were substantially more effective than Pyr-CS at higher polymer:DNA mass ratios and showed a maximum efficiency at 200:1 (50%–70% transfected cells). Overall, the results show the possibility of combining substituent effects in a single carrier, thereby increasing its efficacy. View Full-Text
Keywords: chitosan; polyplex; cell transfection; gene delivery chitosan; polyplex; cell transfection; gene delivery
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MDPI and ACS Style

Badazhkova, V.D.; Raik, S.V.; Polyakov, D.S.; Poshina, D.N.; Skorik, Y.A. Effect of Double Substitution in Cationic Chitosan Derivatives on DNA Transfection Efficiency. Polymers 2020, 12, 1057.

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