Department of Biomedical Engineering, Khalifa University of Science, Technology, and Research, PO Box 127788, Abu Dhabi, United Arab Emirates.
Int J Pharm. 2013 Sep 15;454(1):388-93. doi: 10.1016/j.ijpharm.2013.07.026. Epub 2013 Jul 19.
Reactive oxygen species (ROS) play an important role in the pathogenesis of rheumatoid arthritis (RA). ROS such as hydrogen peroxide and superoxide are overproduced by activated macrophages in RA. As scavengers of ROS, enzymatic proteins such as catalase and superoxide dismutase (SOD) have a great therapeutic potential; however, in vivo application is limited especially when they are orally administered. Although, the oral route is the most convenient for drug administration, therapeutic proteins are easily degraded in vivo by the harsh conditions of gastrointestinal (GI) tract. Here, we introduce a novel drug delivery system composed of zein, a plant storage protein derived from maize. We demonstrate that zein nanoparticles can protect therapeutic proteins, catalase and SOD, from the harsh conditions of GI tract. Folate-conjugated catalase or SOD in zein nanoparticles can target the activated macrophages and scavenge the ROS generated by macrophages in vitro. This novel drug delivery system will be applicable to other orally administered treatments based on the protective property in the harsh conditions of GI tract.
活性氧 (ROS) 在类风湿关节炎 (RA) 的发病机制中起着重要作用。RA 中活化的巨噬细胞会过度产生过氧化氢和超氧阴离子等 ROS。作为 ROS 的清除剂，过氧化氢酶和超氧化物歧化酶 (SOD) 等酶蛋白具有很大的治疗潜力；然而，体内应用受到限制，特别是当它们经口服给药时。尽管口服途径是最方便的给药方式，但治疗性蛋白质在胃肠道 (GI) 道的恶劣条件下很容易在体内降解。在这里，我们介绍了一种由玉米来源的植物储存蛋白玉米醇溶蛋白组成的新型药物递送系统。我们证明玉米醇溶蛋白纳米粒可以保护治疗性蛋白质过氧化氢酶和 SOD 免受 GI 道恶劣条件的影响。叶酸偶联的过氧化氢酶或 SOD 在玉米醇溶蛋白纳米粒中可以靶向活化的巨噬细胞，并清除体外巨噬细胞产生的 ROS。这种新型药物递送系统将适用于其他基于 GI 道恶劣条件下的保护特性的口服治疗方法。
