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透明质酸/褐藻糖胶基纳米粒子作为表没食子儿茶素没食子酸酯递药系统的巨噬细胞靶向载体的研究进展。

The Development of Hyaluronan/Fucoidan-Based Nanoparticles as Macrophages Targeting an Epigallocatechin-3-Gallate Delivery System.

机构信息

Department of Anesthesiology, Show Chwan Memorial Hospital, Changhua 50008, Taiwan.

Faculty of Pharmacy, National Yang-Ming University, Taipei 11221, Taiwan.

出版信息

Int J Mol Sci. 2020 Aug 31;21(17):6327. doi: 10.3390/ijms21176327.

Abstract

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.

摘要

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。

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