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

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.This work was supported by the Spanish Ministry of Science and Innovation (grant number SAF2011-29648) with funds from the European Union, and by the Junta de Andalucia (grant numbers AGR-6826 and CTS 164). Parts of the experiments were financed by funds of the European Regional Development Fund (ERDF) Operative Program of the Region of Murcia 2007–2013. The research contract of Dr A Abel Lozano-Pérez was partially supported (at 80%) by the FEDER Operative Program of the Region of Murcia 2007–2013. F Algieri is a predoctoral fellow of the Junta de Andalucia; J Garrido-Mesa is a predoctoral fellow of the Spanish Ministry of Education, Culture and Sport; N Garrido-Mesa is a postdoctoral fellow of the Ramon Areces Foundation; ME Rodríguez-Cabezas is a postdoctoral fellow of Centro de Investigaciones Biomédicas en Red – Enfermedades Hepáticas y Digest (CIBER-EHD), which is funded by the Instituto de Salud Carlos III