P084 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

Abstract

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. We used a versatile single-step surface-functionalizing 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 sulfate sodium (DSS)-induced colitis. 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. 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).