کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2083978 1545340 2014 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Biodegradable nanoparticles composed of dendrigraft poly-l-lysine for gene delivery
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
Biodegradable nanoparticles composed of dendrigraft poly-l-lysine for gene delivery
چکیده انگلیسی


• We developed a novel gene vector using dendrigraft poly-l-lysine (DGL).
• pDNA/DGL complex (DGL complex) showed the sufficiently high gene expression.
• pDNA/DGL/γ-PGA complex (DGL/γ-PGA complex) decreased the toxicity of DGL complex.
• DGL/γ-PGA complex showed high gene expression comparable to DGL complex.
• DGL/γ-PGA complex showed high gene expression selectively in the spleen.

We developed novel gene vectors composed of dendrigraft poly-l-lysine (DGL). The transgene expression efficiency of the pDNA/DGL complexes (DGL complexes) was markedly higher than that of the control pDNA/poly-l-lysine complex. However, the DGL complexes caused cytotoxicity and erythrocyte agglutination at high doses. Therefore, γ-polyglutamic acid (γ-PGA), which is a biodegradable anionic polymer, was added to the DGL complexes to decrease their toxicity. The resultant ternary complexes (DGL/γ-PGA complexes) were shown to be stable nanoparticles, and those with γ-PGA to pDNA charge ratios of >8 had anionic surface charges. The transgene expression efficiency of the DGL/γ-PGA complexes was similar to that of the DGL complexes; however, they exhibited lower cytotoxicity and did not induce erythrocyte agglutination at high doses. After being intravenously administered to mice, the DGL6 complex demonstrated high transfection efficiency in the liver, lungs, and spleen, whereas the DGL6/γ-PGA8 complex only displayed high transfection efficiency in the spleen. Future studies should examine the utility of DGL and DGL/γ-PGA complexes for clinical gene therapy.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 87, Issue 3, August 2014, Pages 472–479
نویسندگان
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