Department of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia.
School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia.
Drug Dev Res. 2020 Jun;81(4):419-436. doi: 10.1002/ddr.21648. Epub 2020 Feb 12.
Neutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chronic respiratory diseases. In respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, lung cancer and others, there occurs extreme infiltration and activation of neutrophils followed by a cascade of events like oxidative stress and dysregulated cellular proteins that eventually result in apoptosis and tissue damage. Dysregulation of neutrophil effector functions including delayed neutropil apoptosis, increased neutrophil extracellular traps in the pathogenesis of asthma, and chronic obstructive pulmonary disease enable neutrophils as a potential therapeutic target. Accounting to their role in pathogenesis, neutrophils present as an excellent therapeutic target for the treatment of chronic respiratory diseases. This review highlights the current status and the emerging trends in novel drug delivery systems such as nanoparticles, liposomes, microspheres, and other newer nanosystems that can target neutrophils and their molecular pathways, in the airways against infections, inflammation, and cancer. These drug delivery systems are promising in providing sustained drug delivery, reduced therapeutic dose, improved patient compliance, and reduced drug toxicity. In addition, the review also discusses emerging strategies and the future perspectives in neutrophil-based therapy.
中性粒细胞是免疫系统清除炎症和免疫反应中外源性病原体的必需效应细胞。中性粒细胞在慢性呼吸道疾病中发挥重要作用。在哮喘、慢性阻塞性肺疾病、囊性纤维化、肺癌等呼吸道疾病中，中性粒细胞发生极度浸润和激活，随后发生一系列事件，如氧化应激和细胞蛋白失调，最终导致细胞凋亡和组织损伤。中性粒细胞效应功能的失调，包括中性粒细胞凋亡延迟、中性粒细胞胞外诱捕网增加，在哮喘和慢性阻塞性肺疾病的发病机制中，使中性粒细胞成为一个有潜力的治疗靶点。鉴于其在发病机制中的作用，中性粒细胞是治疗慢性呼吸道疾病的一个极好的治疗靶点。本综述强调了新型药物输送系统（如纳米颗粒、脂质体、微球和其他新型纳米系统）的现状和新兴趋势，这些系统可以针对气道中的感染、炎症和癌症靶向中性粒细胞及其分子途径。这些药物输送系统在提供持续的药物输送、减少治疗剂量、提高患者依从性和降低药物毒性方面具有广阔的应用前景。此外，本文还讨论了基于中性粒细胞的治疗的新兴策略和未来展望。
