Department of Anesthesiology, Show Chwan Memorial Hospital, Changhua 50008, Taiwan.
Faculty of Pharmacy, National Yang-Ming University, Taipei 11221, Taiwan.
Int J Mol Sci. 2020 Aug 31;21(17):6327. doi: 10.3390/ijms21176327.
The aim of this study was to develop a macrophage-targeted nanoparticle composed of hyaluronan/fucoidan complexes with polyethylene glycol-gelatin to encapsulate and deliver epigallocatechin-3-gallate (EGCG), a compound that can regulate macrophage activation and pro-inflammatory mediator production. We show that our nanoparticles can successfully bond to macrophages and deliver more EGCG than an EGCG solution treatment, confirming the anti-inflammatory effects of these nanoparticles in lipopolysaccharide-stimulated macrophages. The prepared nanoparticles were established with a small mean particle size (217.00 ± 14.00 nm), an acceptable polydispersity index (0.28 ± 0.07), an acceptable zeta potential value (-33.60 ± 1.30 mV), and a high EGCG loading efficiency (52.08% ± 5.37%). The targeting abilities of CD44 binding were increased as the hyaluronan concentration increased and decreased by adding a competitor CD44 antibody. Moreover, we found that fucoidan treatment significantly reduced macrophage migration after lipopolysaccharide treatment in a dose-responsive manner. In summary, we successfully created macrophage-targeted nanoparticles for effective targeted delivery of EGCG, which should aid in the development of future anti-inflammatory drugs against macrophage-related diseases.
本研究旨在开发一种由透明质酸/褐藻糖胶与聚乙二醇-明胶组成的巨噬细胞靶向纳米粒子,用于包裹和递送表没食子儿茶素没食子酸酯(EGCG),该化合物可调节巨噬细胞的激活和促炎介质的产生。我们表明,我们的纳米粒子可以成功地与巨噬细胞结合,并输送比 EGCG 溶液处理更多的 EGCG,证实了这些纳米粒子在脂多糖刺激的巨噬细胞中的抗炎作用。所制备的纳米粒子具有小的平均粒径(217.00±14.00nm)、可接受的多分散指数(0.28±0.07)、可接受的 zeta 电位值(-33.60±1.30mV)和高的 EGCG 负载效率(52.08%±5.37%)。随着透明质酸浓度的增加,CD44 结合的靶向能力增加,而通过添加竞争 CD44 抗体则降低。此外,我们发现褐藻糖胶处理可显著降低脂多糖处理后的巨噬细胞迁移,呈剂量依赖性。总之,我们成功地创建了巨噬细胞靶向纳米粒子,用于有效靶向递送 EGCG,这有助于开发针对与巨噬细胞相关的疾病的抗炎药物。