Zwitterionic Inhaler with Synergistic Therapeutics for Reprogramming of M2 Macrophage to Pro-Inflammatory Phenotype.
Zwitterionic Inhaler with Synergistic Therapeutics for Reprogramming of M2 Macrophage to Pro-Inflammatory Phenotype.
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具有协同治疗作用的两性离子吸入器可将 M2 巨噬细胞重编程为促炎表型。
DOI：
10.1002/adhm.202300226
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发表时间：
2023
影响因子：
10
通讯作者：
Jung S
中科院分区：
文献类型：
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作者：
Jung S
多种肺部疾病危及生命，巨噬细胞在生理和病理过程中发挥着关键作用。巨噬细胞具有每种促炎/抗炎表型，每种肺部疾病都可能因巨噬细胞过度极化而加重。因此，开发能够介导巨噬细胞表型的方法是治疗肺部疾病的解决方案之一。为了介导巨噬细胞的表型，肺递送系统（PDS）由于其高效和肺部可及性等优点而被广泛使用。然而，讽刺的是，由于粘液层和气道巨噬细胞组成的完美肺部防御系统，它的药物输送效率很低。在这项研究中，合成了两性离子功能化聚丙交酯乙交酯 (PLGA) 可吸入微粒 (ZwPG) 以提高 PDS 的效率。 PLGA表面形成的两性离子薄层具有较高的雾化稳定性，并表现出较高的抗粘液粘附和巨噬细胞逃避能力。作为巨噬细胞的重编程剂，含有地塞米松 (Dex) 和吡非尼酮 (Pir) 的 ZwPG 可对过度极化的 M2 巨噬细胞进行处理。因此，Dex/Pir 的协同作用诱导 M2 巨噬细胞重编程为促炎表型。
Myriad lung diseases are life threatening and macrophages play a key role in both physiological and pathological processes. Macrophages have each pro‐/anti‐inflammatory phenotype, and each lung disease can be aggravated by over‐polarized macrophage. Therefore, development of a method capable of mediating the macrophage phenotype is one of the solutions for lung disease treatment. For mediating the phenotype of macrophages, the pulmonary delivery system (PDS) is widely used due to its advantages, such as high efficiency and accessibility of the lungs. However, it has a low drug delivery efficiency ironically because of the perfect lung defense system consisting of the mucus layer and airway macrophages. In this study, zwitterion‐functionalized poly(lactide‐co‐glycolide) (PLGA) inhalable microparticles (ZwPG) are synthesized to increase the efficiency of the PDS. The thin layer of zwitterions formed on PLGA surface has high nebulizing stability and show high anti‐mucus adhesion and evasion of macrophages. As a reprogramming agent for macrophages, ZwPG containing dexamethasone (Dex) and pirfenidone (Pir) are treated to over‐polarized M2 macrophages. As a result, a synergistic effect of Dex/Pir induces reprogramming of M2 macrophage to pro‐inflammatory phenotypes.