4 CO-DELIVERY OF TNF-α SIRNA AND IL-22 VIA A NANOPARTICLE-IN-HYDROGEL SYSTEM EXERTS SYNERGISTIC THERAPEUTIC EFFECTS AGAINST ULCERATIVE COLITIS. (18th January 2018)

• Record Type: Journal Article
• Authors: Xiao, Bo; Viennois, Emilie; Denning, Tim L; Merlin, Didier
• Is Part Of: Inflammatory bowel diseases. Volume 24(2018)Supplement 1
• Page Start: S8
• Page End: S8
• Publication Date: 2018-01-18
• Subjects: Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1093/ibd/izy019.022
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract: Combination therapy is an emerging approach for treating ulcerative colitis (UC). During the development of UC, TNF-α acts as the major pro-inflammatory cytokine while interleukin-22 (IL-22) plays an important role in preventing mucosal damage. In the present study, we loaded TNF-α siRNA (siTNF) into galactosylated polymeric nanoparticles (NPs). The resultant Gal-siTNF-NPs had a desirable diameter (～261 nm), narrow size distribution and a slightly negative zeta potential (～‒12 mV). These NPs successful mediated the targeted delivery of siTNF to macrophages and efficiently inhibited the expression of TNF-α. We also found that IL-22 could obviously accelerate mucosal healing. Importantly, oral co-administration of Gal-siTNF-NPs and IL-22 encapsulated in a hydrogel (chitosan/alginate) showed a much stronger capacity to promote mucosal healing and down-regulate the expression of pro-inflammatory factors, and thus had much better therapeutic efficacy against UC in a mouse model, compared with single drug-loaded hydrogels. These findings demonstrate that we may be able to improve upon the conventional monotherapy by co-delivering siTNF and IL-22 via this nanoparticle-in-hydrogel system, which offers a simple oral formulation for targeted drug delivery in UC therapy.