In this project, we develop ultra-small (<100 nm), super-stable in gastrointestinal conditions, that can penetrate the mucus layer nanoparticles for oral targeted delivery of natural antioxidants, anti-inflammatory and immunosuppressant drugs to inflamed macrophages.
Inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis are chronic relapsing disorders of the gastrointestinal tract, charac¬terized by chronic inflammation and epithelial injury induced by the uncontrolled activation of the mucosal immune system. Dendritic cells and macrophages are key cells in the inflamed mucosa, which produce large amounts of pro-inflammatory cytokines. The imbalance between pro-inflammatory and anti-inflammatory cytokines impedes the resolution of inflammation, leading to disease perpetuation and tissue destruction. On the other hand, oxidative stress is considered as one of the etiologic factors involved in several signals and symptoms of IBD that include diarrhea, toxic megacolon and abdominal pain. Once the uncontrolled activation of the immune system occurs, oxidative stress is a major contributing factor to tissue injury and ﬁbrosis.
The treatment of IBD is symptomatic, and depending on the stage of the disease, ranges from oral aminosalicylates, anti-inflammatory and immunosuppressant drugs, to endovenous biological agents such as the anti-tumor necrosis factor (TNF)-a antibody infliximab. These treatments have limited benefits, because of their systemic adverse effects displayed during their long-term use.
More efficacious and safer therapies could rely on developing macrophages-targeted drug delivery systems capable of specifically delivering high doses of anti-inflammatory drugs and antioxidants with minimal exposure of healthy or distant tissues via oral administration.
We hope that this approach would reduce the adverse effects, enhance patient adherence, and enhance the efficacy of the current treatments.