کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
600097 1454295 2013 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and characterization of N-ethyl-N’-(3-dimethylaminopropyl)-guanidinyl-polyethylenimine polymers and investigation of their capability to deliver DNA and siRNA in mammalian cells
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی شیمی کلوئیدی و سطحی
پیش نمایش صفحه اول مقاله
Synthesis and characterization of N-ethyl-N’-(3-dimethylaminopropyl)-guanidinyl-polyethylenimine polymers and investigation of their capability to deliver DNA and siRNA in mammalian cells
چکیده انگلیسی


• Trisubstituted guanidinyl-PEI polymers have been synthesized without compromising on total charge.
• Substitution decreased cytotoxicity of bPEI polymer considerably.
• The projected substitution introduced hydrophobicity in the modified polymers.
• One of the formulations, sGP3, efficiently carried pDNA and siRNA inside the mammalian cells.
• Inspite of showing a decrease in buffering capacity, the modified polymers exhibited higher transfection efficiency advocating that buffering is not a sole criterion for efficient transfection.

Recent advancements in polymeric gene delivery have raised the potential of gene therapy as treatment for various acquired and inherited diseases. Here, we report on the synthesis and characterization of N-ethyl-N’-(3-dimethylaminopropyl)-guanidinyl-polyethylenimine (sGP) polymers and investigation of their capability to carry DNA and siRNA in vitro. Zinc triflate-mediated activation of primary amines of branched polyethylenimine (bPEI) followed by reaction with varying amounts of N-ethyl-N’-(3-dimethylaminopropyl) carbodiimide (EDAC) resulted in the generation of a small series of trisubstituted guanidinyl-modified polyethylenimine polymers. Determination of primary amines on modified polymers by TNBS assay revealed 62–84% of the attempted conjugation of EDAC onto bPEI. These modified polymers were shown to condense plasmid DNA and retard its mobility on 0.8% agarose gel. Further, these polymers were evaluated for their capability to carry pDNA into the cells by performing transfection assay on various mammalian cells. All the modified polymer/pDNA complexes exhibited significantly higher levels of gene expression with one of the complexes, sGP3/pDNA complex, displayed ~1.45 to 3.0 orders of magnitude higher transfection efficiency than that observed in the native bPEI and the commercial transfection reagent, Lipofectamine™. The efficacy of sGP3 polymer was further assessed by siRNA delivery, which resulted in ~81% suppression of the target gene. In conclusion, these studies demonstrate the potential of these substituted guanidinyl-modified PEIs as efficient gene delivery vectors.

N-Ethyl-N’-(3-dimethylaminopropyl)-guanidinyl-modified polyethylenimine polymers have been synthesized via zinc triflate activation, physicochemically characterized and evaluated for their transfection efficiency and cell viability on mammalian cells.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Colloids and Surfaces B: Biointerfaces - Volume 109, 1 September 2013, Pages 197–203
نویسندگان
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