Dexamethasone conjugated polyallylamine: Synthesis, characterization, and in vitro transfection and cytotoxicity

Nuclear transportation of genetic materials is a critical step in gene therapy. Human gene therapy is not routine enough in clinic because an effective and safe gene carrier does not exist yet. It is reported that glucocorticoids such as dexamethasone (Dexa) facilitate nuclear transportation of plas...

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Bibliographic Details
Published in:Journal of drug delivery science and technology 2017-08, Vol.40, p.172-179
Main Authors: Malaekeh-Nikouei, Bizhan, Rezaee, Mehdi, Gholami, Leila, Behzad, Minoo, Mohajeri, Mohammad, Kazemi Oskuee, Reza
Format: Article
Language:English
Subjects:
Dexamethasone
Gene delivery
Nanoparticles
Non-viral vectors
Polyallylamine
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Summary:Nuclear transportation of genetic materials is a critical step in gene therapy. Human gene therapy is not routine enough in clinic because an effective and safe gene carrier does not exist yet. It is reported that glucocorticoids such as dexamethasone (Dexa) facilitate nuclear transportation of plasmid DNA or other polynucleotide molecules to the nucleus. This study is aimed to investigate the influences of Dexa on physicochemical properties, cell transfection and toxicity of polyallylamine (PAA). After activation, Dexa mesylate was conjugated to both unmodified PAA and hexyl acrylate-conjugated PAAs (PAA-6c Acr) through a one-step reaction. PAA-Dexa was purified with dialysis against distilled water and then freeze-dried. The physicochemical properties of the synthesized vectors such as buffering capacity, DNA condensing ability, size, and zeta potential were determined. The PAA 15 kDa-based polyplexes showed better cell transfection than those based on PAA65 kDa in Neuro2A cell line. To sum up, transfection activity was improved in two types of the modified vectors including PAA15-6c Acr30%-Dexa5% at lower carrier to pDNA (C/P) ratios and PAA15-6c Acr50%-Dexa10% at higher C/P ratios. Altogether, the modification of PAA and PAA-6c Acr with Dexa significantly reduced their cytotoxicity, but had not guided their cell transfection to a desired point. [Display omitted]
ISSN:1773-2247
DOI:10.1016/j.jddst.2017.05.021