Assessment of polymeric mucin-drug interactions

Mucosal-delivered drugs have to pass through the mucus layer before absorption through the epithelial cell membrane. Although there has been increasing interest in polymeric mucins, a major structural component of mucus, potentially acting as important physiological regulators of mucosal drug absorp...

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Bibliographic Details
Published in:PloS one 2024-06, Vol.19 (6), p.e0306058
Main Authors: Kishimoto, Hisanao, Ridley, Caroline, Inoue, Katsuhisa, Thornton, David J
Format: Article
Language:English
Subjects:
A549 Cells
Absorption
Binding
Biology and Life Sciences
Cell membranes
Clonal deletion
Complications and side effects
CRISPR
Cyclosporin A
Cyclosporine
Cyclosporine - pharmacology
Cytotoxicity
Drug development
Drug interaction
Drug Interactions
Drugs
Epithelial cells
Epithelium
Fluorescence
Humans
Medicine and Health Sciences
Mucin
Mucin 5AC - genetics
Mucin 5AC - metabolism
Mucin-2 - genetics
Mucin-2 - metabolism
Mucin-5B - genetics
Mucin-5B - metabolism
Mucins
Mucins - metabolism
Mucosa
Mucus
Paclitaxel
Paclitaxel - metabolism
Paclitaxel - pharmacology
Peptides
Physical Sciences
Physiological aspects
Physiology
Protein Binding
Rifampin
Rifampin - pharmacology
Sedimentation & deposition
Theophylline
Viscoelasticity
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Summary:Mucosal-delivered drugs have to pass through the mucus layer before absorption through the epithelial cell membrane. Although there has been increasing interest in polymeric mucins, a major structural component of mucus, potentially acting as important physiological regulators of mucosal drug absorption, there are no reports that have systematically evaluated the interaction between mucins and drugs. In this study, we assessed the potential interaction between human polymeric mucins (MUC2, MUC5B, and MUC5AC) and various drugs with different chemical profiles by simple centrifugal method and fluorescence analysis. We found that paclitaxel, rifampicin, and theophylline likely induce the aggregation of MUC5B and/or MUC2. In addition, we showed that the binding affinity of drugs for polymeric mucins varied, not only between individual drugs but also among mucin subtypes. Furthermore, we demonstrated that deletion of MUC5AC and MUC5B in A549 cells increased the cytotoxic effects of cyclosporin A and paclitaxel, likely due to loss of mucin-drug interaction. In conclusion, our results indicate the necessity to determine the binding of drugs to mucins and their potential impact on the mucin network property.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0306058