Intestinal anti-inflammatory effects of RGD-functionalized silk fibroin nanoparticles in trinitrobenzenesulfonic acid-induced experimental colitis in rats

Rodriguez-Nogales, A. ; Algieri, F. ; De Matteis, L. ; Lozano-Perez, A. ; Garrido-Mesa, J. ; Vezza, T. ; Martínez de la Fuente, J. (Universidad de Zaragoza) ; Cenis, J.L. ; Gálvez, J. ; Rodriguez-Cabezas, M.

Resumen: 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. Purpose: 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. Materials and 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]-1ß, 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). Conclusion: SFNs displayed intestinal anti-inflammatory properties in the TNBS model of colitis in rats, which were improved by functionalization with the RGD peptide.

Idioma: Inglés

DOI: 10.2147/IJN.S116479

Año: 2016

Publicado en: International Journal of Nanomedicine 11 (2016), 5945-5958
ISSN: 1176-9114

Factor impacto JCR: 4.3 (2016)

Categ. JCR: PHARMACOLOGY & PHARMACY rank: 37 / 256 = 0.145 (2016) - Q1 - T1
Categ. JCR: NANOSCIENCE & NANOTECHNOLOGY rank: 29 / 87 = 0.333 (2016) - Q2 - T2

Factor impacto SCIMAGO: 1.173 - Bioengineering (Q1) - Biomaterials (Q1) - Biophysics (Q1) - Organic Chemistry (Q1) - Medicine (miscellaneous) (Q1) - Drug Discovery (Q1) - Nanoscience and Nanotechnology (Q2)

Financiación: info:eu-repo/grantAgreement/ES/MINECO/AGL2015-67995-C3-3-R
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2014-54763-C2-2-R

Tipo y forma: Article (Published version)

Área (Departamento): Área Química Orgánica (Dpto. Química Orgánica)