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Research Article

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

    Mingzhen Zhang

    *Author for correspondence:

    E-mail Address: mzhang21@gsu.edu

    Institute for Biomedical Sciences, Center for Diagnostics & Therapeutics, Georgia State University, Atlanta, GA 30302, USA

    ,
    Xiaoyu Wang

    Food Science & Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA

    ,
    Moon Kwon Han

    Institute for Biomedical Sciences, Center for Diagnostics & Therapeutics, Georgia State University, Atlanta, GA 30302, USA

    ,
    James F Collins

    Food Science & Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA

    &
    Didier Merlin

    Institute for Biomedical Sciences, Center for Diagnostics & Therapeutics, Georgia State University, Atlanta, GA 30302, USA

    Alanta Veterans Affairs Medical Center, Decatur, GA 30033, USA

    Published Online:https://doi.org/10.2217/nnm-2017-0196

    Aim: 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. Materials & methods: 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. Results: Orally administered siRNA-CD98/GDLVs were effectively targeted specifically to colon tissues, resulting in reduced expression of CD98. Conclusion: 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.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1 Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu. Rev. Immunol. 28, 573–621 (2010).
    • 2 Vavricka SR, Gubler M, Gantenbein C et al. Anti-TNF treatment for extraintestinal manifestations of inflammatory bowel disease in the swiss IBD cohort study. Inflamm. Bowel Dis. 23(7), 1174–1181 (2017).
    • 3 Bernstein CN, Blanchard JF, Kliewer E, Wajda A. Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer 91(4), 854–862 (2001).
    • 4 Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 48(4), 526–535 (2001).
    • 5 Neurath MF. Current and emerging therapeutic targets for IBD. Nat. Rev. Gastroenterol. Hepatol. 14(5), 269–278 (2017).
    • 6 Sam JJ, Bernstein CN, Razik R, Thanabalan R, Nguyen GC. Physicians’ perceptions of risks and practices in venous thromboembolism prophylaxis in inflammatory bowel disease. Dig. Dis. Sci. 58(1), 46–52 (2013).
    • 7 Kumar J, Newton A. Colon targeted rifaximin nanosuspension for the treatment of inflammatory bowel disease (IBD). Antiinflamm. Antiallergy Agents Med. Chem. 15(2), 101–117 (2016).
    • 8 Razanskaite V, Bettey M, Downey L et al. Biosimilar infliximab in inflammatory bowel disease: outcomes of a managed switching programme. J. Crohns Colitis 11(6), 690–696 (2017).
    • 9 Dong R, Zheng S, Chen G. The appropriate dose and cost of iron replacement therapy in patients with IBD. Gut 66(1), 196–197 (2017).
    • 10 Ghosh S, Louis E, Beaugerie L et al. Development of the IBD disk: a visual self-administered tool for assessing disability in inflammatory bowel diseases. Inflamm. Bowel Dis. 23(3), 333–340 (2017).
    • 11 Walker JR, Ediger JP, Graff LA et al. The Manitoba IBD cohort study: a population-based study of the prevalence of lifetime and 12 month anxiety and mood disorders. Am. J. Gastroenterol. 103(8), 1989–1997 (2008).
    • 12 Deepak P, Sifuentes H, Sherid M, Stobaugh D, Sadozai Y, Ehrenpreis ED. T-cell non-Hodgkin's lymphomas reported to the FDA AERS with tumor necrosis factor-alpha (TNF-alpha) inhibitors: results of the REFURBISH study. Am. J. Gastroenterol. 108(1), 99–105 (2013).
    • 13 Nielsen OH, Loftus EV Jr, Jess T. Safety of TNF-alpha inhibitors during IBD pregnancy: a systematic review. BMC Med. 11, 174 (2013).
    • 14 Fiorino G, Danese S, Pariente B, Allez M. Paradoxical immune-mediated inflammation in inflammatory bowel disease patients receiving anti-TNF-alpha agents. Autoimmun. Rev. 13(1), 15–19 (2014).
    • 15 Laroui H, Geem D, Xiao B et al. Targeting intestinal inflammation with CD98 siRNA/PEI-loaded nanoparticles. Mol. Ther. 22(1), 69–80 (2014). • Describes a synthetic nanoparticle to delivery CD98 siRNA to decrease colitis.
    • 16 Maisel K, Ensign L, Reddy M, Cone R, Hanes J. Effect of surface chemistry on nanoparticle interaction with gastrointestinal mucus and distribution in the gastrointestinal tract following oral and rectal administration in the mouse. J. Control. Release 197, 48–57 (2015).
    • 17 Zhang MZ, Xu CL, Wen LQ et al. A Hyaluronidase-responsive nanoparticle-based drug delivery system for targeting colon cancer cells. Cancer Res. 76(24), 7208–7218 (2016).
    • 18 Xiao B, Zhang Z, Viennois E et al. Combination therapy for ulcerative colitis: orally targeted nanoparticles prevent mucosal damage and relieve inflammation. Theranostics 6(12), 2250–2266 (2016).
    • 19 Zhang MZ, Yu Y, Yu RN, Wan M, Zhang RY, Zhao YD. Tracking the down-regulation of folate receptor-alpha in cancer cells through target specific delivery of quantum dots coupled with antisense oligonucleotide and targeted peptide. Small 9(24), 4183–4193 (2013).
    • 20 Zhang MZ, Li C, Fang BY et al. High transfection efficiency of quantum dot-antisense oligonucleotide nanoparticles in cancer cells through dual-receptor synergistic targeting. Nanotechnology 25(25), 255102 (2014).
    • 21 Laroui H, Viennois E, Xiao B et al. Fab'-bearing siRNA TNF alpha-loaded nanoparticles targeted to colonic macrophages offer an effective therapy for experimental colitis. J. Control. Release 186, 41–53 (2014).
    • 22 Huang Z, Gan JJ, Jia LX et al. An orally administrated nucleotide-delivery vehicle targeting colonic macrophages for the treatment of inflammatory bowel disease. Biomaterials 48, 26–36 (2015).
    • 23 Zhang M, Viennois E, Prasad M et al. Edible ginger-derived nanoparticles: a novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer. Biomaterials 101, 321–340 (2016).
    • 24 Zhang MZ, Collins JF, Merlin D. Do ginger-derived nanoparticles represent an attractive treatment strategy for inflammatory bowel diseases? Nanomedicine 11(23), 3035–3037 (2016).
    • 25 Hang TTN, Dalmasso G, Torkvist L et al. CD98 expression modulates intestinal homeostasis, inflammation, and colitis-associated cancer in mice. J. Clin. Invest. 121(5), 1733–1747 (2011).
    • 26 Rietbergen MM, Martens-De Kemp SR, Bloemena E et al. Cancer stem cell enrichment marker CD98: A prognostic factor for survival in patients with human papillomavirus-positive oropharyngeal cancer. Eur. J. Cancer 50(4), 765–773 (2014).
    • 27 Kucharzik T, Lugering A, Yan YT et al. Activation of epithelial CD98 glycoprotein perpetuates colonic inflammation. Lab. Invest. 85(7), 932–941 (2005).
    • 28 Sussman DA, Santaolalla R, Strobel S et al. Cancer in inflammatory bowel disease: lessons from animal models. Curr. Opin. Gastroen. 28(4), 327–333 (2012).
    • 29 Sun CC, Zargham R, Shao Q et al. Association of CD98, integrin beta 1, integrin beta 3 and Fak with the progression and liver metastases of colorectal cancer. Pathol. Res. Pract. 210(10), 668–674 (2014).
    • 30 Mu JY, Zhuang XY, Wang QL et al. Interspecies communication between plant and mouse gut host cells through edible plant derived exosome-like nanoparticles. Mol. Nutr. Food Res. 58(7), 1561–1573 (2014).
    • 31 Kansas state University. Kansas Lipidomics Research Center. www.k-state.edu/lipid/lipidomics/profiling.html.
    • 32 Zhang MZ, Xiao B, Wang H et al. Edible ginger-derived nano-lipids loaded with doxorubicin as a novel drug-delivery approach for colon cancer therapy. Mol. Ther. 24(10), 1783–1796 (2016). •• Provides detailed information about how to prepare ginger-derived nanolipids for chemotherapy-doxorubicin delivery.
    • 33 Ju SW, Mu JY, Dokland T et al. Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis. Mol. Ther. 21(7), 1345–1357 (2013).
    • 34 Zhuang XY, Teng Y, Samykutty A et al. Grapefruit-derived nanovectors delivering therapeutic miR17 through an intranasal route inhibit brain tumor progression. Mol. Ther. 24(1), 96–105 (2016). • Describes an miRNA delivery system based on grapefruit-derived lipids.
    • 35 Yang JS, Gad H, Lee SY et al. A role for phosphatidic acid in COPI vesicle fission yields insights into Golgi maintenance. Nat. Cell Biol. 10(10), 1146–1153 (2008).
    • 36 Kooijman EE, Chupin V, de Kruijff B, Burger KNJ. Modulation of membrane curvature by phosphatidic acid and lysophosphatidic acid. Traffic 4(3), 162–174 (2003).
    • 37 Popova AV, Hincha DK. Effects of flavonol glycosides on liposome stability during freezing and drying. BBA Biomembranes 1858(12), 3050–3060 (2016).
    • 38 Tam YY, Chen S, Cullis PR. Advances in lipid nanoparticles for siRNA delivery. Pharmaceutics 5(3), 498–507 (2013). •• Gives a detailed description of current situation of lipid nanoparticles for siRNA delivery.
    • 39 Foged C. siRNA delivery with lipid-based systems: promises and pitfalls. Curr. Top. Med. Chem. 12(2), 97–107 (2012).
    • 40 Srinivas R, Samanta S, Chaudhuri A. Cationic amphiphiles: promising carriers of genetic materials in gene therapy. Chem. Soc. Rev. 38(12), 3326–3338 (2009).
    • 41 Zhang MZ, Viennois E, Xu CL, Merlin D. Plant derived edible nanoparticles as a new therapeutic approach against diseases. Tissue Barriers 4(2), e1134415 (2016).
    • 42 Yang SY, Zheng Y, Chen JY et al. Comprehensive study of cationic liposomes composed of DC-Chol and cholesterol with different mole ratios for gene transfection. Colloid Surf. B 101, 6–13 (2013).
    • 43 Sato A, Takagi M, Shimamoto A et al. Small interfering RNA delivery to the liver by intravenous administration of galactosylated cationic liposomes in mice. Biomaterials 28(7), 1434–1442 (2007).
    • 44 Kawakami S, Yamashita F, Nishikawa M et al. Asialoglycoprotein receptor-mediated gene transfer using novel galactosylated cationic liposomes. Biochem. Bioph. Res. Commun. 252(1), 78–83 (1998).
    • 45 Desigaux L, Sainlos M, Lambert O et al. Self-assembled lamellar complexes of siRNA with lipidic aminoglycoside derivatives promote efficient siRNA delivery and interference. Proc. Natl Acad. Sci. USA 104(42), 16534–16539 (2007).
    • 46 Li LY, Hou JJ, Liu XJ et al. Nucleolin-targeting liposomes guided by aptamer AS1411 for the delivery of siRNA for the treatment of malignant melanomas. Biomaterials 35(12), 3840–3850 (2014).
    • 47 Xiao B, Laroui H, Viennois E et al. Nanoparticles with surface antibody against CD98 and carrying CD98 small interfering RNA reduce colitis in mice. Gastroenterology 146(5), 1289–1300 (2014). • Showed that regulated CD98 expression by CD98 siRNA was a reliable way to reduce colitis in mice.