The role of mucus in cell-based models used to screen mucosal drug delivery

Abstract

The increasing interest in developing tools to predict drug absorption through mucosal surfaces is fostering the establishment of epithelial cell-based models. Cell-based in vitro techniques for drug permeability assessment are less laborious, cheaper and address the concerns of using laboratory animals. Simultaneously, in vitro barrier models that thoroughly simulate human epithelia or mucosae may provide useful data to speed up the entrance of new drugs and new drug products into the clinics. Nevertheless, standard cell-based in vitro models that intend to reproduce epithelial surfaces often discard the role of mucus in influencing drug permeation/absorption. Biomimetic models of mucosae in which mucus production has been considered may not be able to fully reproduce the amount and architecture of mucus, resulting in biased characterization of permeability/absorption. In these cases, artificial mucus may be used to supplement cell-based models but still proper identification and quantification are required. In this review, considerations regarding the relevance of mucus in the development of cell-based epithelial and mucosal models mimicking the gastro-intestinal tract, the cervico-vaginal tract and the respiratory tract, and the impact of mucus on the permeability mechanisms are addressed. From simple epithelial monolayers to more complex 3D structures, the impact of the presence of mucus for the extrapolation to the in vivo scenario is critically analyzed. Finally, an overview is provided on several techniques and methods to characterize the mucus layer over cell-based barriers, in order to intimately reproduce human mucosal layer and thereby, improve in vitro/in vivo correlation.

Mucoadhesive chitosan-coated PLGA nanoparticles for oral delivery of ferulic acid

“…In order to select drugs and evaluate their intestinal absorption potential, many in vitro models have been studied and used [41]. These models present advantages when compared to the in vivo tests of intestinal permeability, since besides being less laborious and with lower costs, they also present benefits on ethical issues [42].…”

In situ-Like Aerosol Inhalation Exposure for Cytotoxicity Assessment Using Airway-on-Chips Platforms

“…Following perfusion of PBS, NHBE cells were fixed within the devices and inserts using 4% PFA (Sigma-Aldrich, 47608) for 20 min at RT and were washed again three times with PBS. For detection of glycoproteins typically present in mucus (Leonard et al, 2010;Lechanteur et al, 2018), samples were treated with 10 mg/ml alcian Blue 8G× (Sigma-Aldrich, A5268) in 3% acetic acid (1% w/v) for 15 min at RT and were washed three times with PBS. Images were then acquired with a light inverted microscope (Nikon Eclipse TS100) at 10×.…”

Review of recently used techniques and materials to improve the efficiency of orally administered proteins/peptides

“…The primary role of the mucosal layer is the regulation of pH at the lumen surface and thus results in the formation of an acidic microenvironment [28]. The mucosal layer has different thickness and turnover values regarding the anatomical position, pathophysiological status and interaction with the external environment [29]. Generally, the mucous layer acts as a physical barrier as a result of its negative charges and lipophilic nature, whereas the general hydrophilicity of mucus also acts as an interactive barrier, which retards the movement of the molecules within and through the mucus.…”