title: Intestinal anti-inflammatory effects of RGD-functionalized silk fibroin nanoparticles in trinitrobenzenesulfonic acid-induced experimental colitis in rats.
abstract: BACKGROUND
  Current treatment of inflammatory bowel disease is based on the use of immunosuppressants or anti-inflammatory drugs, which are characterized by important side effects that can limit their use. Previous research has been performed by administering these drugs as nanoparticles that target the ulcerated intestinal regions and increase their bioavailability. It has been reported that silk fibroin can act as a drug carrier and shows anti-inflammatory properties.
  
  
  OBJECTIVE
  This study was designed to enhance the interaction of the silk fibroin nanoparticles (SFNs) with the injured intestinal tissue by functionalizing them with the peptide motif RGD (arginine-glycine-aspartic acid) and to evaluate the intestinal anti-inflammatory properties of these RGD-functionalized silk fibroin nanoparticles (RGD-SFNs) in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis.
  
  
  METHODS
  SFNs were prepared by nanoprecipitation in methanol, and the linear RGD peptide was linked to SFNs using glutaraldehyde as the crosslinker. The SFNs (1 mg/rat) and RGD-SFNs (1 mg/rat) were administered intrarectally to TNBS-induced colitic rats for 7 days.
  
  
  RESULTS
  The SFN treatments ameliorated the colonic damage, reduced neutrophil infiltration, and improved the compromised oxidative status of the colon. However, only the rats treated with RGD-SFNs showed a significant reduction in the expression of different pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, and IL-12) and inducible nitric oxide synthase in comparison with the TNBS control group. Moreover, the expression of both cytokine-induced neutrophil chemoattractant-1 and monocyte chemotactic protein-1 was significantly diminished by the RGD-SFN treatment. However, both treatments improved the intestinal wall integrity by increasing the gene expression of some of its markers (trefoil factor-3 and mucins).
  
  
  CONCLUSIONS
  SFNs displayed intestinal anti-inflammatory properties in the TNBS model of colitis in rats, which were improved by functionalization with the RGD peptide.
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research, University of Granada, Granada.
authors.forename: Alba
authors.initials: A
authors.lastname: Rodriguez-Nogales
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research, University of Granada, Granada.
authors.forename: Francesca
authors.initials: F
authors.lastname: Algieri
authors.affiliation: Instituto de Nanociencia de Aragón, Universidad de Zaragoza, Zaragoza.
authors.forename: Laura
authors.initials: L
authors.lastname: De Matteis
authors.affiliation: Department of Biotechnology, Instituto Murciano de Investigación y Desarrollo Agrario y Alimentario, Murcia, Spain.
authors.forename: A Abel
authors.initials: AA
authors.lastname: Lozano-Perez
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research, University of Granada, Granada.
authors.forename: Jose
authors.initials: J
authors.lastname: Garrido-Mesa
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research, University of Granada, Granada.
authors.forename: Teresa
authors.initials: T
authors.lastname: Vezza
authors.affiliation: Instituto de Nanociencia de Aragón, Universidad de Zaragoza, Zaragoza.
authors.forename: J M
authors.initials: JM
authors.lastname: de la Fuente
authors.affiliation: Department of Biotechnology, Instituto Murciano de Investigación y Desarrollo Agrario y Alimentario, Murcia, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Cenis
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research, University of Granada, Granada.
authors.forename: Julio
authors.initials: J
authors.lastname: Gálvez
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research, University of Granada, Granada.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Rodriguez-Cabezas
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005349:Fibroins / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000276:immunology; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D014302:Trinitrobenzenesulfonic Acid; D005349:Fibroins; D052247:Nitric Oxide Synthase Type II
keywords: RGD; TNBS rat colitis; inflammatory bowel disease; nanoparticles; silk fibroin