Orally targeted galactosylated chitosan poly(lactic-co-glycolic acid) nanoparticles loaded with TNF-ɑ siRNA provide a novel strategy for the experimental treatment of ulcerative colitis.

The current treatments used in inflammatory bowel disease (IBD) therapy have significant side effects. Thus, it is very necessary to position and release TNF-α siRNA in inflamed tissues. Here, we demonstrate that poly(lactic-co-glycolic acid) can pack TNF-α siRNA efficiently into nanoparticles (NPs), and galactosylated chitosan (GC) can be grafted onto the NP surface, improving the RAW 264.7 macrophage-targeting kinetics of the NPs in vitro. Next, we orally administered GC-modified NPs loaded with TNF-α siRNA to C57BL/6 mice treated with 3% dextran sodium sulfate (DSS) to investigate their use in the treatment of colitis. When TNF-α siRNA loaded NPs were released into the colitis tissues of mice, GC-modified NPs (GPNs) alleviated the inflammation more efficiently than unmodified PGLA NPs (PNs). A series of colitis parameters (e.g., weight loss, myeloperoxidase (MPO) activity) demonstrated that GPNs have better anti-inflammatory effects than PNs. As indicated by flow cytometry, grafting GC onto NPs increased the macrophage uptake capacity and improved the kinetics of endocytosis. Collectively, our findings indicate that GC- modified TNF-α siRNA loaded NPs are powerful and efficient nanoscale materials for the delivery of therapeutic molecules to colitis tissues.