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

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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

Titel: Effect of Double Substitution in Cationic Chitosan Derivatives on DNA Transfection Efficiency
Författare: Badazhkova, Veronika D.; Raik, Sergei; Polyakov, Dmitry S.; Poshina, Daria N.; Skorik, Yury A.
Upphovmannens organisation: Division of Pharmaceutical Biosciences
Datum: 2020-05
Språk: eng
Sidantal: 15
Tillhör serie: Polymers
ISSN: 2073-4360
DOI: https://doi.org/10.3390/polym12051057
Permanenta länken (URI): http://hdl.handle.net/10138/317893
Abstrakt: 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.
Subject: chitosan
cell transfection
gene delivery
1182 Biochemistry, cell and molecular biology
317 Pharmacy
Referentgranskad: Ja
Licens: cc_by
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion

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