Rodriguez-Nogales A, Lozano-Pérez A A, Aznar-Cervantes S D, Algieri F, Garrido-Mesa J, Garrido-Mesa N, Vezza T, Utrilla M P, Cenis J L, Rodríguez-Cabezas M E, Gálvez J
CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Avenida del Conocimiento s/n, 18100 Armilla Granada, Spain.
Instituto Murciano de Investigación y Desarrollo Agrario y Alimentario (IMIDA), c/Mayor, 1, 30150 La Alberca, Murcia, Spain.
Int J Pharm. 2016 Sep 10;511(1):1-9. doi: 10.1016/j.ijpharm.2016.06.120. Epub 2016 Jun 27.
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.
丝素蛋白(SF)具有抗炎特性并能促进伤口愈合。此外,由于丝素蛋白颗粒能够将化合物递送至受损的结肠组织,因此可作为抗肠道炎症活性药物的载体。本研究评估了丝素蛋白在类似于人类肠道炎症的大鼠三硝基苯磺酸结肠炎模型中的作用。通过两种技术,以两种颗粒形式经直肠途径给予丝素蛋白(8mg/kg),一种是通过喷雾干燥制成微粒,另一种是在有机溶剂中脱溶剂制备纳米颗粒,同时以水溶液形式口服给药。丝素蛋白治疗改善了结肠损伤,减少了中性粒细胞浸润,并改善了结肠受损的氧化状态。它们还降低了促炎细胞因子如IL-1β和抗炎细胞因子IL-10的基因表达。此外,它们通过增加一些标志物(绒毛蛋白、三叶因子-3和粘蛋白)的基因表达改善了肠壁完整性,从而加速了愈合。丝素蛋白颗粒的免疫调节特性也在体外巨噬细胞中进行了测试:它们在基础条件下激活免疫反应,在促炎刺激后不会增强免疫反应。总之,丝素蛋白颗粒可作为载体,将活性药物递送至受损的肠道结肠,并具有额外的抗炎和愈合特性。