Effect of aqueous and particulate silk fibroin in a rat model of experimental colitis

Int J Pharm. 2016 Sep 10;511(1):1-9. doi: 10.1016/j.ijpharm.2016.06.120. Epub 2016 Jun 27.

Abstract

Silk fibroin (SF) has anti-inflammatory properties and promotes wound healing. Moreover, SF particles act as carriers of active drugs against intestinal inflammation due to their capacity to deliver the compound to the damaged colonic tissue. The present work assesses the effect of SF in the trinitrobenzenesulfonic acid model of rat colitis that resembles human intestinal inflammation. SF (8mg/kg) was administered in aqueous solution orally and in two particulate formats by intrarectal route, following two technologies: spray drying to make microparticles and desolvation in organic solvent to produce nanoparticles. SF treatments ameliorated the colonic damage, reduced neutrophil infiltration and improved the compromised oxidative status of the colon. They also reduced the gene expression of pro-inflammatory cytokines like IL-1β and the anti-inflammatory cytokine IL-10. Moreover, they improved the intestinal wall integrity by increasing the gene expression of some of its markers (villin, trefoil factor-3 and mucins), thus accelerating the healing. The immunomodulatory properties of SF particles were also tested in vitro in macrophages: they activated the immune response in basal conditions without increasing it after a pro-inflammatory insult. In conclusion, SF particles could be useful as carriers to deliver active drugs to the damaged intestinal colon with additional anti-inflammatory and healing properties.

Keywords: Drug carrier; Immunomodulation; Microparticles; Nanoparticles; Silk fibroin; TNBS rat colitis.

MeSH terms

  • Animals
  • Bombyx
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Colitis / pathology
  • Disease Models, Animal*
  • Fibroins / administration & dosage*
  • Fibroins / chemistry
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / metabolism
  • Mice
  • Rats
  • Silk / administration & dosage*
  • Silk / chemistry
  • Treatment Outcome
  • Water / administration & dosage*
  • Water / chemistry

Substances

  • Inflammation Mediators
  • Silk
  • Water
  • Fibroins