Airway mucus in pulmonary diseases: Muco-adhesive and muco-penetrating particles to overcome the airway mucus barriers.
Airway mucus in pulmonary diseases: Muco-adhesive and muco-penetrating particles to overcome the airway mucus barriers.
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DOI：
10.1016/j.ijpharm.2023.122661
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发表时间：
2023-02
影响因子：
5.8
通讯作者：
R. Pangeni;Tuo Meng;Sagun Poudel;Divya Sharma;Hallie Hutsell;Jonathan Ma;B. Rubin;Worth Longest;M. Hindle;Qingguo Xu
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文献类型：
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作者：
R. Pangeni;Tuo Meng;Sagun Poudel;Divya Sharma;Hallie Hutsell;Jonathan Ma;B. Rubin;Worth Longest;M. Hindle;Qingguo Xu
气道粘液是一种复杂的粘弹性凝胶，它通过捕获吸入的外来病原体并促进其通过粘膜纤毛清除（MCC）而提供防御性物理屏障并屏蔽气道上皮。在患有呼吸系统疾病（如慢性阻塞性肺病（COPD）、囊性纤维化（CF）、非CF支气管扩张和哮喘）的患者中，粘蛋白聚合物的交联和物理缠结的增加以及粘液脱水通常改变并通常减小粘液网状网络孔径，这减少了嗜中性粒细胞迁移，减少了病原体捕获，维持了细菌感染，并加速了肺功能下降。含有疏水性药物的常规气溶胶颗粒被MCC快速捕获和去除。因此，设计具有适当尺寸和表面化学性质的气雾剂递送系统至关重要，其可以改善药物保留和吸收，目的是提高功效。可生物降解的粘膜粘附颗粒（MAP）和粘膜穿透颗粒（MPP）已经被工程化以实现有效的肺部递送并延长药物在肺部的停留时间。MAP可用于靶向粘液，因为它们通过空间阻塞和/或粘附被捕获在气道粘液中。MPP避免粘膜粘附，并且被设计成具有小于粘液网络的粒度，从而增强颗粒的肺滞留以及向呼吸道上皮层的运输和药物吸收。在这篇综述中，我们的目的是提供洞察气道粘液的组成，在健康和患病的受试者的气道粘液的流变学特性，最新的技术来研究气道粘液的流动动力学和颗粒扩散（特别是，多粒子跟踪，MPT），和工程MPPs的进展，有助于改善气道粘液的渗透，肺分布和保留。
Airway mucus is a complex viscoelastic gel that provides a defensive physical barrier and shields the airway epithelium by trapping inhaled foreign pathogens and facilitating their removalviamucociliary clearance (MCC). In patients with respiratory diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), non-CF bronchiectasis, and asthma, an increase in crosslinking and physical entanglement of mucin polymers as well as mucus dehydration often alters and typically reduces mucus mesh network pore size, which reduces neutrophil migration, decreases pathogen capture, sustains bacterial infection, and accelerates lung function decline. Conventional aerosol particles containing hydrophobic drugs are rapidly captured and removed by MCC. Therefore, it is critical to design aerosol delivery systems with the appropriate size and surface chemistry that can improve drug retention and absorption with the goal of increased efficacy. Biodegradable muco-adhesive particles (MAPs) and muco-penetrating particles (MPPs) have been engineered to achieve effective pulmonary delivery and extend drug residence time in the lungs. MAPs can be used to target mucus as they get trapped in airway mucus by steric obstruction and/or adhesion. MPPs avoid muco-adhesion and are designed to have a particle size smaller than the mucus network, enhancing lung retention of particles as well as transport to the respiratory epithelial layer and drug absorption. In this review, we aim to provide insight into the composition of airway mucus, rheological characteristics of airway mucus in healthy and diseased subjects, the most recent techniques to study the flow dynamics and particle diffusion in airway mucus (in particular, multiple particle tracking, MPT), and the advancements in engineering MPPs that have contributed to improved airway mucus penetration, lung distribution, and retention.