title: Dual TNF-α/Cyclin D1 Gene Silencing With an Oral Polymeric Microparticle System as a Novel Strategy for the Treatment of Inflammatory Bowel Disease.
abstract: OBJECTIVE
  RNA silencing utilizing short interfering RNA (siRNA) offers a new and exciting means to overcome the limitations of current treatment options of many diseases. However, delivery of these molecules still poses a great challenge to date.
  
  
  METHODS
  In the present study, a multicompartmental biodegradable polymer-based nanoparticles-in-microsphere oral system (NiMOS) using gelatin nanoparticles encapsulating a combination of siRNA duplexes specifically targeted against tumor necrosis factor-α (TNF-α) and cyclin D1 (Ccnd1) was employed to study its effects on a dextran sulfate sodium (DSS)-induced acute colitis mouse model mimicking inflammatory bowel disease (IBD). DSS colitis-bearing animals were divided into several control and treatment groups and received either no treatment, blank NiMOS, NiMOS-encapsulating inactive (scrambled), active TNF-α silencing, CyD1 silencing siRNA, or a combination of both active siRNAs by repeated oral administration of three NiMOS doses.
  
  
  RESULTS
  Successful gene silencing with the aid of dual siRNA treatment led to decreased colonic levels of TNF-α or CyD1, suppressed expression of certain pro-inflammatory cytokines (interleukin-1α and -β, interferon-γ), an increase in body weight, and reduced tissue myeloperoxidase activity, while the silencing effect of CyD1 siRNA or the dual treatment was more potent than that of TNF-α siRNA alone.
  
  
  CONCLUSIONS
  Results of this study demonstrate the therapeutic potential of a NiMOS-based oral combined TNF-α and CyD1 gene silencing system for the treatment of IBD as shown in an acute colitis model.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Kriegel
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Amiji