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Non-Cellular Layers of the Respiratory Tract: Protection against Pathogens and Target for Drug Delivery

Journal

PHARMACEUTICS
Volume 14, Issue 5, Pages -

Publisher

MDPI
DOI: 10.3390/pharmaceutics14050992

Keywords

epithelial barriers; respiratory tract; mucus; pulmonary surfactant; drug delivery; mucociliary clearance; mucopermeation; mucoadhesion

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Epithelial barriers are important for maintaining homeostasis by separating the human body from the environment. The respiratory barrier, compared to other barriers like the skin and gastrointestinal tract, is the thinnest and least protective. Understanding the properties of epithelial cells and non-cellular layers can help determine the permeability of the respiratory barrier and its interactions with gases, pathogens, and drugs.
Epithelial barriers separate the human body from the environment to maintain homeostasis. Compared to the skin and gastrointestinal tract, the respiratory barrier is the thinnest and least protective. The properties of the epithelial cells (height, number of layers, intercellular junctions) and non-cellular layers, mucus in the conducting airways and surfactant in the respiratory parts determine the permeability of the barrier. The review focuses on the non-cellular layers and describes the architecture of the mucus and surfactant followed by interaction with gases and pathogens. While the penetration of gases into the respiratory tract is mainly determined by their hydrophobicity, pathogens use different mechanisms to invade the respiratory tract. Often, the combination of mucus adhesion and subsequent permeation of the mucus mesh is used. Similar mechanisms are also employed to improve drug delivery across the respiratory barrier. Depending on the payload and target region, various mucus-targeting delivery systems have been developed. It appears that the mucus-targeting strategy has to be selected according to the planned application.

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