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- Title
Assessment of polymeric mucin–drug interactions.
- Authors
Kishimoto, Hisanao; Ridley, Caroline; Inoue, Katsuhisa; Thornton, David J.
- Abstract
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.
- Subjects
CYCLOSPORINE; ALKALOIDS; POLYMERIC drugs; RIFAMPIN; MUCINS; FLUORIMETRY; DRUG absorption; PACLITAXEL
- Publication
PLoS ONE, 2024, Vol 19, Issue 6, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0306058