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

• Authors: Mingzhan Zhang, Georgia State University; Emilie Viennois, Georgia State University; Meena Prasad, Emory University; Yunchen Zhang, Georgia State University; Lixin Wang, Georgia State University; Zhan Zhang, Georgia State University; Moon Kwon Han, Georgia State University; Bo Xiao, Georgia State University; Changlong Xu, Georgia State University; Shanthi Srinivasan, Emory University; Didier Merlin, Georgia State University
• Journal Title: Biomaterials
• Volume: Volume 101
• Publisher: Elsevier | 2016-09-01, Pages 321-340
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.biomaterials.2016.06.018
• Subjects: Health Sciences, General
• Keywords: Science & Technology; Technology; Engineering, Biomedical; Materials Science, Biomaterials; Engineering; Materials Science; Edible ginger derived nanoparticles; Inflammatory bowel disease; Colitis-associated cancer; Natural drug delivery system; Therapy; EXOSOME-LIKE NANOPARTICLES; CHRONIC INTESTINAL INFLAMMATION; COLORECTAL-CANCER; COLON-CANCER; ULCERATIVE-COLITIS; T-CELLS; BARRIER FUNCTION; POLYMERIC NANOPARTICLES; LOADED NANOPARTICLES; PROSTATE-CANCER

Abstract

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.