The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA.
Expert Opin Drug Deliv. 2021 May;18(5):595-606. doi: 10.1080/17425247.2021.1854222. Epub 2020 Dec 7.
: Airway mucus gel layer serves as a key delivery barrier that limits the performance of inhaled drug delivery nanoparticles. Conventional nanoparticles are readily trapped by the airway mucus and rapidly cleared from the lung via mucus clearance mechanisms. These nanoparticles cannot distribute throughout the lung airways, long-reside in the lung and/or reach the airway epithelium. To address this challenge, strategies to enhance particle penetration through the airway mucus have been developed and proof-of-concept has been established using mucus model systems..: In this review, we first overview the biochemical and biophysical characteristics that render the airway mucus a challenging delivery barrier. We then introduce strategies to improve particle penetration through the airway mucus. Specifically, we walk through two classes of approaches, including modification of physicochemical properties of nanoparticles and modulation of barrier properties of airway mucus.: State-of-the-art strategies to overcome the airway mucus barrier have been introduced and experimentally validated. However, data should be interpreted in the comprehensive context of therapeutic delivery from the site of administration to the final destination to determine clinically-relevant approaches. Further, safety should be carefully monitored, particularly when it comes to mucus-altering strategies that may perturb physiological functions of airway mucus.
: 气道黏液凝胶层作为一个关键的输送屏障，限制了吸入式药物输送纳米颗粒的性能。传统的纳米颗粒很容易被气道黏液捕获，并通过黏液清除机制迅速从肺部清除。这些纳米颗粒不能分布在整个肺部气道中，不能在肺部长时间停留和/或到达气道上皮。为了解决这个挑战，已经开发了增强粒子穿透气道黏液的策略，并使用黏液模型系统证明了其概念。: 在这篇综述中，我们首先概述了使气道黏液成为具有挑战性的输送屏障的生化和物理特性。然后，我们介绍了改善粒子穿透气道黏液的策略。具体来说，我们介绍了两类方法，包括纳米颗粒物理化学性质的修饰和气道黏液屏障性质的调节。: 已经引入了克服气道黏液屏障的最新策略，并进行了实验验证。然而，应该从给药部位到最终目的地的治疗输送的综合角度来解释数据，以确定临床相关的方法。此外，应该仔细监测安全性，特别是对于可能扰乱气道黏液生理功能的改变黏液的策略。
