کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1423604 1509027 2016 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Colonic gene silencing using siRNA-loaded calcium phosphate/PLGA nanoparticles ameliorates intestinal inflammation in vivo
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
Colonic gene silencing using siRNA-loaded calcium phosphate/PLGA nanoparticles ameliorates intestinal inflammation in vivo
چکیده انگلیسی

Cytokines and chemokines are predominant players in the progression of inflammatory bowel diseases. While systemic neutralization of these players with antibodies works well in some patients, serious contraindications and side effects have been reported. Therefore, the local interference of cytokine signaling mediated by siRNA-loaded nanoparticles might be a promising new therapeutic approach. In this study, we produced multi-shell nanoparticles consisting of a calcium phosphate (CaP) core coated with siRNA directed against pro-inflammatory mediators, encapsulated into poly(d,l-lactide-co-glycolide acid) (PLGA), and coated with a final outer layer of polyethyleneimine (PEI), for the local therapeutic treatment of colonic inflammation. In cell culture, siRNA-loaded CaP/PLGA nanoparticles exhibited a rapid cellular uptake, almost no toxicity, and an excellent in vitro gene silencing efficiency. Importantly, intrarectal application of these nanoparticles loaded with siRNA directed against TNF-α, KC or IP-10 to mice suffering from dextran sulfate sodium (DSS)-induced colonic inflammation led to a significant decrease of the target genes in colonic biopsies and mesenteric lymph nodes which was accompanied with a distinct amelioration of intestinal inflammation. Thus, this study provides evidence that the specific and local modulation of the inflammatory response by CaP/PLGA nanoparticle-mediated siRNA delivery could be a promising approach for the treatment of intestinal inflammation.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 222, 28 January 2016, Pages 86–96
نویسندگان
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