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Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats

Authors Lozano-Pérez AA, Rodriguez-Nogales A, Ortiz-Cullera V, Algieri F, Garrido-Mesa J, Zorrilla P, Rodriguez-Cabezas ME, Garrido-Mesa N, Utrilla MP, De Matteis L, de la Fuente JM, Cenis JL, Gálvez J

Received 28 May 2014

Accepted for publication 10 July 2014

Published 23 September 2014 Volume 2014:9(1) Pages 4507—4520

DOI https://doi.org/10.2147/IJN.S68526

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Antonio Abel Lozano-Pérez,1 Alba Rodriguez-Nogales,2 Víctor Ortiz-Cullera,1 Francesca Algieri,2 José Garrido-Mesa,2 Pedro Zorrilla,2 M Elena Rodriguez-Cabezas,2 Natividad Garrido-Mesa,2 M Pilar Utrilla,2 Laura De Matteis,3 Jesús Martínez de la Fuente,3 José Luis Cenis,1 Julio Gálvez2

1Instituto Murciano de Investigación y Desarrollo Agrario y Alimentario, Murcia, Spain; 2Centro de Investigaciones Biomédicas en Red – Enfermedades Hepáticas y Digestivas, Department of Pharmacology, ibs Granada, Center for Biomedical Research, University of Granada, Granada, Spain; 3Instituto de Nanociencia de Aragón, Universidad de Zaragoza, Zaragoza, Spain

Purpose: We aimed to evaluate the intestinal anti-inflammatory properties of silk fibroin nanoparticles, around 100 nm in size, when loaded with the stilbene compound resveratrol, in an experimental model of rat colitis.
Methods: Nanoparticles were loaded with resveratrol by adsorption. The biological effects of the resveratrol-loaded nanoparticles were tested both in vitro, in a cell culture of RAW 264.7 cells (mouse macrophages), and in vivo, in the trinitrobenzenesulfonic acid model of rat colitis, when administered intracolonically.
Results: The resveratrol liberation in 1× phosphate-buffered saline (PBS; pH 7.4) was characterized by fast liberation, reaching the solubility limit in 3 hours, which was maintained over a period of 80 hours. The in vitro assays revealed immunomodulatory properties exerted by these resveratrol-loaded nanoparticles since they promoted macrophage activity in basal conditions and inhibited this activity when stimulated with lipopolysaccharide. The in vivo experiments showed that after evaluation of the macroscopic symptoms, inflammatory markers, and intestinal barrier function, the fibroin nanoparticles loaded with resveratrol had a better effect than the single treatments, being similar to that produced by the glucocorticoid dexamethasone.
Conclusion: Silk fibroin nanoparticles constitute an attractive strategy for the controlled release of resveratrol, showing immunomodulatory properties and intestinal anti-inflammatory effects.

Keywords: immunomodulatory, cytokines, TNBS rat colitis, RAW 264.7 macrophage cells, antioxidant

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