ABSTRACT

Introduction: 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..

Areas covered: 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.

Expert opinion: 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.

摘要

简介：气道粘液凝胶层是限制吸入给药纳米颗粒性能的关键输送屏障。传统的纳米颗粒很容易被气道粘液捕获，并通过粘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气道、长期驻留在肺中和/或到达气道上皮。为了应对这一挑战，已经制定了增强颗粒通过气道粘液穿透的策略，并使用粘液模型系统建立了概念验证。

涵盖的领域：在这篇综述中，我们首先概述了使气道粘液成为具有挑战性的输送屏障的生化和生物物理特征。然后，我们介绍了改善颗粒通过气道粘液穿透的策略。具体来说，我们介绍了两类方法，包括改变纳米粒子的物理化学性质和调节气道粘液的屏障特性。

专家意见：已经引入并通过实验验证了克服气道粘液屏障的最先进的策略。然而，数据应该在从给药部位到最终目的地的治疗递送的综合背景下进行解释，以确定临床相关的方法。此外，应仔细监测安全性，特别是在涉及可能扰乱气道粘液生理功能的粘液改变策略时。