Department of Life Sciences, University of Trieste, Via L. Giorgieri 5, I-34127, Trieste, Italy.
Department of Micro- and Nanotechnology, Technical University of Denmark, Building 345C, 2800, Kgs. Lyngby, Denmark.
Macromol Biosci. 2017 Nov;17(11). doi: 10.1002/mabi.201700214. Epub 2017 Sep 4.
Tissue damage caused by excessive amounts of neutrophil-derived reactive oxygen species (ROS) occurs in many inflammatory diseases. Butyrate is a short-chain fatty acid (SCFA) with known anti-inflammatory properties, able to modulate several neutrophil functions. Evidence is provided here that butyrate inhibits neutrophil ROS release in a dose and time-dependent fashion. Given the short half-life of butyrate, chitosan/hyaluronan nanoparticles are next designed and developed as controlled release carriers able to provide cells with a long-lasting supply of this SCFA. Notably, while the inhibition of neutrophil ROS production by free butyrate declines over time, that of butyrate-loaded chitosan/hyaluronan nanoparticles (B-NPs) is sustained. Additional valuable features of these nanoparticles are inherent ROS scavenger activity, resistance to cell internalization, and mucoadhesiveness. B-NPs appear as promising tools to limit ROS-dependent tissue injury during inflammation. Particularly, by virtue of their mucoadhesiveness, B-NPs administered by enema can be effective in the treatment of inflammatory bowel diseases.
在许多炎症性疾病中,过量中性粒细胞衍生的活性氧(ROS)会导致组织损伤。丁酸盐是一种具有已知抗炎特性的短链脂肪酸(SCFA),能够调节多种中性粒细胞功能。本文提供的证据表明,丁酸盐以剂量和时间依赖的方式抑制中性粒细胞 ROS 的释放。鉴于丁酸盐的半衰期短,接下来设计并开发了壳聚糖/透明质酸纳米粒子作为控制释放载体,能够为细胞提供这种 SCFA 的持久供应。值得注意的是,虽然游离丁酸盐抑制中性粒细胞 ROS 产生的作用会随时间减弱,但负载丁酸盐的壳聚糖/透明质酸纳米粒子(B-NPs)的抑制作用是持续的。这些纳米粒子的其他有价值的特性是固有 ROS 清除活性、抵抗细胞内化和黏膜黏附性。B-NPs 似乎是限制炎症过程中 ROS 依赖性组织损伤的有前途的工具。特别是,由于其黏膜黏附性,通过灌肠给予 B-NPs 可以有效治疗炎症性肠病。