Oral Delivery of Nanoparticles Loaded With Ginger Active Compound, 6-Shogaol, Attenuates Ulcerative Colitis and Promotes Wound Healing in a Murine Model of Ulcerative Colitis

J Crohns Colitis. 2018 Jan 24;12(2):217-229. doi: 10.1093/ecco-jcc/jjx115.

Abstract

Background and aims: Oral drug delivery is the most attractive pathway for ulcerative colitis [UC] therapy, since it has many advantages. However, this strategy has encountered many challenges, including the instability of drugs in the gastrointestinal tract [GT], low targeting of disease tissues, and severe adverse effects. Nanoparticles capable of colitis tissue-targeted delivery and site-specific drug release may offer a unique and therapeutically effective system that addresses these formidable challenges.

Methods: We used a versatile single-step surface-functionalising technique to prepare PLGA/PLA-PEG-FA nanoparticles loaded with the ginger active compound, 6-shogaol [NPs-PEG-FA/6-shogaol]. The therapeutic efficacy of NPs-PEG-FA/6-shogaol was evaluated in the well-established mouse model of dextran sulphate sodium [DSS]-induced colitis.

Results: NPs-PEG-FA exhibited very good biocompatibility both in vitro and in vivo. Subsequent cellular uptake experiments demonstrated that NPs-PEG-FA could undergo efficient receptor-mediated uptake by colon-26 cells and activated Raw 264.7 macrophage cells. In vivo, oral administration of NPs-PEG-FA/6-shogaol encapsulated in a hydrogel system [chitosan/alginate] significantly alleviated colitis symptoms and accelerated colitis wound repair in DSS-treated mice by regulating the expression levels of pro-inflammatory [TNF-α, IL-6, IL-1β, and iNOS] and anti-inflammatory [Nrf-2 and HO-1] factors.

Conclusions: Our study demonstrates a convenient, orally administered 6-shogaol drug delivery system that effectively targets colitis tissue, alleviates colitis symptoms, and accelerates colitis wound repair. This system may represent a promising therapeutic approach for treating inflammatory bowel disease [IBD].

Keywords: Ulcerative colitis; drug delivery system; therapy.

MeSH terms

  • Alginates / administration & dosage
  • Animals
  • Biocompatible Materials / administration & dosage
  • Catechols / administration & dosage*
  • Catechols / pharmacology
  • Cell Line
  • Chitosan / administration & dosage
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / metabolism*
  • Colitis, Ulcerative / pathology
  • Dextran Sulfate
  • Disease Models, Animal
  • Drug Delivery Systems
  • Epithelial Cells / metabolism
  • Folic Acid / administration & dosage
  • Glucuronic Acid / administration & dosage
  • Heme Oxygenase-1 / genetics
  • Hexuronic Acids / administration & dosage
  • Hydrogels
  • Interleukin-1beta / genetics
  • Interleukin-6 / genetics
  • Intestinal Mucosa / metabolism
  • Macrophages / metabolism
  • Membrane Proteins / genetics
  • Mice
  • NF-E2-Related Factor 2 / genetics
  • Nanoparticles*
  • Nitric Oxide Synthase Type II / genetics
  • Polyethylene Glycols / administration & dosage
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Wound Healing / drug effects*

Substances

  • Alginates
  • Biocompatible Materials
  • Catechols
  • Hexuronic Acids
  • Hydrogels
  • IL1B protein, mouse
  • Interleukin-1beta
  • Interleukin-6
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Polyethylene Glycols
  • shogaol
  • Glucuronic Acid
  • Chitosan
  • Dextran Sulfate
  • Folic Acid
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Heme Oxygenase-1
  • Hmox1 protein, mouse