{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:10:14Z","timestamp":1784092214418,"version":"3.55.0"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005865","name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005865","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JSPS KAKENHI","award":["21K06695"],"award-info":[{"award-number":["21K06695"]}]},{"name":"The Helen Muir Fund"},{"name":"The Wellcome Centre for Cell-Matrix Research is supported by core funding from Wellcome","award":["203128\/A\/16\/Z"],"award-info":[{"award-number":["203128\/A\/16\/Z"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1371\/journal.pone.0306058","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T18:22:17Z","timestamp":1719512537000},"page":"e0306058","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Assessment of polymeric mucin\u2013drug interactions"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7580-6864","authenticated-orcid":true,"given":"Hisanao","family":"Kishimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Ridley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhisa","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7148-1970","authenticated-orcid":true,"given":"David J.","family":"Thornton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"pone.0306058.ref001","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nrmicro2538","article-title":"Mucin dynamics and enteric pathogens","volume":"9","author":"MA McGuckin","year":"2011","journal-title":"Nat Rev Microbiol"},{"key":"pone.0306058.ref002","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1146\/annurev.physiol.70.113006.100702","article-title":"Structure and function of the polymeric mucins in airways mucus","volume":"70","author":"DJ Thornton","year":"2008","journal-title":"Annu Rev Physiol"},{"key":"pone.0306058.ref003","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.addr.2008.09.008","article-title":"Barrier properties of mucus","volume":"61","author":"RA Cone","year":"2009","journal-title":"Adv Drug Deliv Rev"},{"key":"pone.0306058.ref004","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.ijpharm.2017.09.018","article-title":"Physicochemical properties of mucus and their impact on transmucosal drug delivery","volume":"532","author":"J Leal","year":"2017","journal-title":"Int J Pharm"},{"key":"pone.0306058.ref005","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/mi.2008.5","article-title":"Mucins in the mucosal barrier to infection","volume":"1","author":"SK Linden","year":"2008","journal-title":"Mucosal Immunol"},{"key":"pone.0306058.ref006","doi-asserted-by":"crossref","first-page":"113845","DOI":"10.1016\/j.addr.2021.113845","article-title":"Purified mucins in drug delivery research","volume":"178","author":"M Marczynski","year":"2021","journal-title":"Adv Drug Deliv Rev"},{"key":"pone.0306058.ref007","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.3390\/pharmaceutics15122714","article-title":"Advances in the Evaluation of Gastrointestinal Absorption Considering the Mucus Layer","volume":"15","author":"K Miyazaki","year":"2023","journal-title":"Pharmaceutics"},{"key":"pone.0306058.ref008","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.addr.2017.10.009","article-title":"The role of mucus on drug transport and its potential to affect therapeutic outcomes","volume":"124","author":"X Murgia","year":"2018","journal-title":"Adv Drug Deliv Rev"},{"key":"pone.0306058.ref009","doi-asserted-by":"crossref","DOI":"10.1007\/s11095-019-2701-9","article-title":"Mucins are involved in the intestinal permeation of lipophilic drugs in the proximal region of rat small intestine","volume":"36","author":"K Miyazaki","year":"2019","journal-title":"Pharm. 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