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      Oral administration of ginger-derived nanolipids loaded with siRNA as a novel approach for efficient siRNA drug delivery to treat ulcerative colitis

      1 , 2 , 1 , 2 , 1 , 3
      Nanomedicine
      Future Medicine Ltd

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          Abstract

          <div class="section"> <a class="named-anchor" id="d7474245e191"> <!-- named anchor --> </a> <h5 class="section-title" id="d7474245e192">Aim:</h5> <p id="d7474245e194">To develop novel siRNA delivery system overcoming the limitations of synthetic nanoparticles, such as potential side effects, nonspecificity and economic production for ulcerative colitis therapy. </p> </div><div class="section"> <a class="named-anchor" id="d7474245e196"> <!-- named anchor --> </a> <h5 class="section-title" id="d7474245e197">Materials &amp; methods:</h5> <p id="d7474245e199">Nanoparticles composed of edible ginger-derived lipid, termed ginger-derived lipid vehicles (GDLVs) were generated from ginger lipids through hydration of a lipid film, a commonly used method for a liposome fabrication. The morphology, biocompatibility and transfection efficiency of GDLVs loaded with siRNA-CD98 (siRNA-CD98/GDLVs) were characterized by standard methods. </p> </div><div class="section"> <a class="named-anchor" id="d7474245e201"> <!-- named anchor --> </a> <h5 class="section-title" id="d7474245e202">Results:</h5> <p id="d7474245e204">Orally administered siRNA-CD98/GDLVs were effectively targeted specifically to colon tissues, resulting in reduced expression of CD98. </p> </div><div class="section"> <a class="named-anchor" id="d7474245e206"> <!-- named anchor --> </a> <h5 class="section-title" id="d7474245e207">Conclusion:</h5> <p id="d7474245e209">These GDLVs have great promise as efficient siRNA-delivery vehicles while potentially obviating issues related to the traditional synthetic nanoparticles. As such, they help shift the current paradigm of siRNA delivery away from artificially synthesized nanoparticles toward the use of naturally derived nanovehicles from edible plants. </p> </div>

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          Most cited references39

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          Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer.

          There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. In this study, we characterized a specific population of nanoparticles derived from edible ginger (GDNPs 2) and demonstrated their efficient colon targeting following oral administration. GDNPs 2 had an average size of ∼230 nm and exhibited a negative zeta potential. These nanoparticles contained high levels of lipids, a few proteins, ∼125 microRNAs (miRNAs), and large amounts of ginger bioactive constituents (6-gingerol and 6-shogaol). We also demonstrated that GDNPs 2 were mainly taken up by intestinal epithelial cells (IECs) and macrophages, and were nontoxic. Using different mouse colitis models, we showed that GDNPs 2 reduced acute colitis, enhanced intestinal repair, and prevented chronic colitis and colitis-associated cancer (CAC). 2D-DIGE/MS analyses further identified molecular target candidates of GDNPs 2 involved in these mouse models. Oral administration of GDNPs 2 increased the survival and proliferation of IECs and reduced the pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), and increased the anti-inflammatory cytokines (IL-10 and IL-22) in colitis models, suggesting that GDNPs 2 has the potential to attenuate damaging factors while promoting the healing effect. In conclusion, GDNPs 2, nanoparticles derived from edible ginger, represent a novel, natural delivery mechanism for improving IBD prevention and treatment with an added benefit of overcoming limitations such as potential toxicity and limited production scale that are common with synthetic nanoparticles.
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            Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis.

            Food-derived exosome-like nanoparticles pass through the intestinal tract throughout our lives, but little is known about their impact or function. Here, as a proof of concept, we show that the cells targeted by grape exosome-like nanoparticles (GELNs) are intestinal stem cells whose responses underlie the GELN-mediated intestinal tissue remodeling and protection against dextran sulfate sodium (DSS)-induced colitis. This finding is further supported by the fact that coculturing of crypt or sorted Lgr5⁺ stem cells with GELNs markedly improved organoid formation. GELN lipids play a role in induction of Lgr5⁺ stem cells, and the liposome-like nanoparticles (LLNs) assembled with lipids from GELNs are required for in vivo targeting of intestinal stem cells. Blocking β-catenin-mediated signaling pathways of GELN recipient cells attenuates the production of Lgr5⁺ stem cells. Thus, GELNs not only modulate intestinal tissue renewal processes, but can participate in the remodeling of it in response to pathological triggers.
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              Current and emerging therapeutic targets for IBD

              The management of IBD has undergone major advances with the development of biologic agents. Here, Markus Neurath provides an overview of current and future therapeutic targets for IBD, including insights into the mechanisms and rationale behind such approaches.
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                Author and article information

                Journal
                Nanomedicine
                Nanomedicine
                Future Medicine Ltd
                1743-5889
                1748-6963
                August 2017
                August 2017
                : 12
                : 16
                : 1927-1943
                Affiliations
                [1 ]Institute for Biomedical Sciences, Center for Diagnostics &amp; Therapeutics, Georgia State University, Atlanta, GA 30302, USA
                [2 ]Food Science &amp; Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA
                [3 ]Alanta Veterans Affairs Medical Center, Decatur, GA 30033, USA
                Article
                10.2217/nnm-2017-0196
                5827822
                28665164
                b0c2f6f3-1e3b-4a97-bc85-cd6835e5ee16
                © 2017
                History

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