Department of Pharmaceutics, Shanghai Eighth People's Hospital, Shanghai 200235, China.
Int J Pharm. 2013 Jun 5;449(1-2):37-43. doi: 10.1016/j.ijpharm.2013.04.008. Epub 2013 Apr 12.
The aim of this study was to investigate the use of N-acetylglucosamine (NAG) to accelerate drug release from a lectin-modified carrier. A wheat germ agglutinin (WGA)-anchored salmeterol xinafoate (SalX)-loaded nanoparticles-in-microparticles system (NiMS) was prepared with an ionotropic gelation technique combined with a spray drying method. The formulated microparticles were spherical, with diameters ranging mainly from 2 to 8 μm; the drug entrapment efficiency was >70% (w/w), and the loading capacity was approximately 8% (w/w). Drug release from WGA-SalX-NiMS, within the first 4h, was approximately 30% less than that from SalX-NiMS, indicating an effect of lectin-modification to retard drug release from the NiMS. Due to "sugar-lectin" interactions, drug release from WGA-SalX-NiMS was substantially increased after the addition of NAG to the release medium. However, no significant influence of NAG was observed on the drug release profile of SalX-NiMS without WGA anchorage. The characteristics of NAG-WGA interaction may provide valuable insights into the "triggering-effects" of specific sugars on drug release from lectin-anchored carriers. These results suggest that it is possible to control drug release from a lectin-anchored drug delivery system using a specific sugar, and that the designed novel WGA-SalX-NiMS may be a suitable formulation for chronotherapy of asthma.
本研究旨在探讨 N-乙酰氨基葡萄糖（NAG）在加速糖蛋白修饰载体中药物释放的应用。采用离子凝胶化技术结合喷雾干燥法制备了小麦胚凝集素（WGA）锚定的沙美特罗昔萘酸酯（SalX）载药纳米粒-微球系统（NiMS）。所制备的微球为球形，直径主要分布在 2-8μm 之间；药物包封效率>70%（w/w），载药量约为 8%（w/w）。与 SalX-NiMS 相比，WGA-SalX-NiMS 在最初 4h 内的药物释放量约减少 30%，表明糖蛋白修饰可延缓 NiMS 中的药物释放。由于“糖-糖蛋白”相互作用，当向释放介质中添加 NAG 后，WGA-SalX-NiMS 中的药物释放显著增加。然而，对于没有 WGA 锚定的 SalX-NiMS，NAG 对药物释放曲线没有明显影响。NAG-WGA 相互作用的特点可能为特定糖对糖蛋白锚定载体中药物释放的“触发效应”提供有价值的见解。这些结果表明，使用特定糖可以控制糖蛋白锚定的药物传递系统中的药物释放，并且设计的新型 WGA-SalX-NiMS 可能是治疗哮喘的时间治疗的合适制剂。
