کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1427110 986848 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Electrophoretic purification of tumor-targeted polyethylenimine-based polyplexes reduces toxic side effects in vivo
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
Electrophoretic purification of tumor-targeted polyethylenimine-based polyplexes reduces toxic side effects in vivo
چکیده انگلیسی

Non-viral vectors based on polyethylenimine (PEI) are usually generated with an excess of PEI. However, the amount of unbound polymer correlates with toxicity limiting the in vivo use of these gene carriers. Purification based on size exclusion chromatography of PEI/DNA polyplexes smaller than 200 nm has been shown to efficiently remove unbound PEI polymer. A novel purification method based on electrophoresis can purify PEI polyplexes independent of their size resulting in polyplexes with final PEI nitrogen/DNA phosphate ratios between 2.6 and 3.1. Also unbound PEI conjugates like PEGylated PEI and transferrin-conjugated PEI can be separated from the polyplexes, providing formulations with clearly defined compositions. Purified polyplexes can mediate in vitro gene transfer with high transfection efficiencies while demonstrating lower cellular toxicity. Purified polyplexes were well-tolerated when systemically delivered into tumor-bearing mice at 100 μg/20 g body weight, with tumor gene expression levels up to 5-fold higher than the non-purified polyplexes. Mice receiving non-purified gene carriers exhibited severe toxicity leading to high mortality and unfavourable gene expression patterns.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 122, Issue 3, 8 October 2007, Pages 236–245
نویسندگان
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