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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0306058 |
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| author | Hisanao Kishimoto Caroline Ridley Katsuhisa Inoue David J Thornton |
| author_facet | Hisanao Kishimoto Caroline Ridley Katsuhisa Inoue David J Thornton |
| author_sort | Hisanao Kishimoto |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-976c5176187a41b4a60b30cdc424519b |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-976c5176187a41b4a60b30cdc424519b2025-08-20T01:52:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01196e030605810.1371/journal.pone.0306058Assessment of polymeric mucin-drug interactions.Hisanao KishimotoCaroline RidleyKatsuhisa InoueDavid J ThorntonMucosal-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.https://doi.org/10.1371/journal.pone.0306058 |
| spellingShingle | Hisanao Kishimoto Caroline Ridley Katsuhisa Inoue David J Thornton Assessment of polymeric mucin-drug interactions. PLoS ONE |
| title | Assessment of polymeric mucin-drug interactions. |
| title_full | Assessment of polymeric mucin-drug interactions. |
| title_fullStr | Assessment of polymeric mucin-drug interactions. |
| title_full_unstemmed | Assessment of polymeric mucin-drug interactions. |
| title_short | Assessment of polymeric mucin-drug interactions. |
| title_sort | assessment of polymeric mucin drug interactions |
| url | https://doi.org/10.1371/journal.pone.0306058 |
| work_keys_str_mv | AT hisanaokishimoto assessmentofpolymericmucindruginteractions AT carolineridley assessmentofpolymericmucindruginteractions AT katsuhisainoue assessmentofpolymericmucindruginteractions AT davidjthornton assessmentofpolymericmucindruginteractions |