کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2481600 1556244 2010 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
PEGylation of biodegradable dextran nanogels for siRNA delivery
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
PEGylation of biodegradable dextran nanogels for siRNA delivery
چکیده انگلیسی

Delivering intact small interfering RNA (siRNA) into the cytoplasm of targeted cells in vivo is considered a major obstacle in the development of clinically applicable RNA interference-based therapies. Although dextran hydroxyethyl methacrylate (dex-HEMA) nanogels have been reported to be suitable carriers for siRNA delivery in vitro, and are ideally sized (approximately 180 nm) for intravenous delivery to tumors, they likely possess insufficient blood circulation times to enable an adequate extravasation and accumulation in the tumor tissue. PEGylation of these nanogels should not only improve their circulation time but also minimize their aggregation upon intravenous injection. For this reason, a new type of nanogels and three different methods of PEGylating dextran nanogels were evaluated. Covalent PEGylation of the siRNA-loaded nanogels using N-hydroxysuccinimidyl polyethylene glycol (NHS-PEG) was shown to be superior to the addition of both polyethylene glycol (PEG) and PEG grafted poly-l-glutamic acid (PGA-PEG). Flow cytometry and confocal microscopy revealed that PEGylated nanogels are still taken up efficiently by HuH-7 human hepatoma cells and A431 human epithelial carcinoma cells and that the process is cell type dependent. Moreover, PEGylated nanogels loaded with siRNA cause significant EGFP knockdown in a human hepatoma cell line (HuH-7_EGFP) and are non-toxic for these cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutical Sciences - Volume 40, Issue 4, 11 July 2010, Pages 342–351
نویسندگان
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