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

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dc.contributor.author Badazhkova, Veronika D.
dc.contributor.author Raik, Sergei
dc.contributor.author Polyakov, Dmitry S.
dc.contributor.author Poshina, Daria N.
dc.contributor.author Skorik, Yury A.
dc.date.accessioned 2020-07-23T12:47:01Z
dc.date.available 2020-07-23T12:47:01Z
dc.date.issued 2020-05
dc.identifier.citation Badazhkova , V D , Raik , S , Polyakov , D S , Poshina , D N & Skorik , Y A 2020 , ' Effect of Double Substitution in Cationic Chitosan Derivatives on DNA Transfection Efficiency ' , Polymers , vol. 12 , no. 5 , 1057 . https://doi.org/10.3390/polym12051057
dc.identifier.other PURE: 141078622
dc.identifier.other PURE UUID: 0c8fc9ee-d6de-45fc-bdf3-8d6ecb231476
dc.identifier.other WOS: 000541431100062
dc.identifier.uri http://hdl.handle.net/10138/317893
dc.description.abstract 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 H-1 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. en
dc.format.extent 15
dc.language.iso eng
dc.relation.ispartof Polymers
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject chitosan
dc.subject polyplex
dc.subject cell transfection
dc.subject gene delivery
dc.subject GENE-THERAPY
dc.subject PROTON-SPONGE
dc.subject IN-VITRO
dc.subject DELIVERY
dc.subject POLYPLEXES
dc.subject VECTORS
dc.subject MECHANISM
dc.subject 1182 Biochemistry, cell and molecular biology
dc.subject 317 Pharmacy
dc.title Effect of Double Substitution in Cationic Chitosan Derivatives on DNA Transfection Efficiency en
dc.type Article
dc.contributor.organization Division of Pharmaceutical Biosciences
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.3390/polym12051057
dc.relation.issn 2073-4360
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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