Choline and geranate ionic liquid for subgingival biofilm control
[Display omitted] •Choline and geranate (CAGE) ionic liquid showed promise in treating subgingival infection.•Periodontal pathogens were killed by CAGE-induced cell membrane disruption.•CAGE overcame extracellular matrix, a physical barrier of biofilms that attenuates drug diffusion.•Subgingival bio...
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Veröffentlicht in: | International journal of pharmaceutics 2024-09, Vol.662, p.124544, Article 124544 |
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container_title | International journal of pharmaceutics |
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creator | Yan, Chunyang Nakajima, Mayuka Ikeda-Imafuku, Mayumi Yanagawa, Mayuko Hayatsu, Manabu Fukuta, Tatsuya Shibata, Shinsuke Mitragotri, Samir Tabeta, Koichi |
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•Choline and geranate (CAGE) ionic liquid showed promise in treating subgingival infection.•Periodontal pathogens were killed by CAGE-induced cell membrane disruption.•CAGE overcame extracellular matrix, a physical barrier of biofilms that attenuates drug diffusion.•Subgingival biofilms were neutralized and eventually destroyed by CAGE treatment.
Periodontitis is a chronic inflammatory disease that causes destruction of the periodontium and eventual tooth loss. The priority in the periodontal treatment is to remove the subgingival biofilm. Chemical removal of biofilms using antimicrobial agents has been applied in clinical practice. However, their clinical effect is still limited because the agents must overcome biofilm’s significant drug tolerance, which is primarily caused by the extracellular matrix, a physical barrier that attenuates drug diffusion. This study aimed to study the use of ionic liquids (ILs), a new class of biocompatible materials, for controlling subgingival biofilms because of their excellent permeability. Choline and geranate (CAGE) IL was tested for its highly potent antiseptic behavior and permeability. Antibacterial tests revealed that the significant efficacy of CAGE against periodontopathic microorganisms was derived from their ability to destroy cell membrane, as demonstrated by membrane permeability assay and transmission electron microscopy imaging. Antibiofilm tests using two pathogenic biofilm models revealed that CAGE exerted efficacy against the biofilm-embedded bacteria, conspicuously neutralized the biofilms, and eventually destroyed the biofilm structure. Furthermore, the penetration of CAGE into the biofilm was visually confirmed using confocal laser scanning microscopy. This study highlighted the potential of CAGE as a powerful antibiofilm therapeutic. |
doi_str_mv | 10.1016/j.ijpharm.2024.124544 |
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•Choline and geranate (CAGE) ionic liquid showed promise in treating subgingival infection.•Periodontal pathogens were killed by CAGE-induced cell membrane disruption.•CAGE overcame extracellular matrix, a physical barrier of biofilms that attenuates drug diffusion.•Subgingival biofilms were neutralized and eventually destroyed by CAGE treatment.
Periodontitis is a chronic inflammatory disease that causes destruction of the periodontium and eventual tooth loss. The priority in the periodontal treatment is to remove the subgingival biofilm. Chemical removal of biofilms using antimicrobial agents has been applied in clinical practice. However, their clinical effect is still limited because the agents must overcome biofilm’s significant drug tolerance, which is primarily caused by the extracellular matrix, a physical barrier that attenuates drug diffusion. This study aimed to study the use of ionic liquids (ILs), a new class of biocompatible materials, for controlling subgingival biofilms because of their excellent permeability. Choline and geranate (CAGE) IL was tested for its highly potent antiseptic behavior and permeability. Antibacterial tests revealed that the significant efficacy of CAGE against periodontopathic microorganisms was derived from their ability to destroy cell membrane, as demonstrated by membrane permeability assay and transmission electron microscopy imaging. Antibiofilm tests using two pathogenic biofilm models revealed that CAGE exerted efficacy against the biofilm-embedded bacteria, conspicuously neutralized the biofilms, and eventually destroyed the biofilm structure. Furthermore, the penetration of CAGE into the biofilm was visually confirmed using confocal laser scanning microscopy. This study highlighted the potential of CAGE as a powerful antibiofilm therapeutic.</description><identifier>ISSN: 0378-5173</identifier><identifier>ISSN: 1873-3476</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2024.124544</identifier><identifier>PMID: 39094920</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Biocompatible materials ; Drug tolerance ; Extracellular matrix ; Ionic liquid ; Periodontal pocket ; Permeability</subject><ispartof>International journal of pharmaceutics, 2024-09, Vol.662, p.124544, Article 124544</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c290t-8fadaf08fe0d95a4584da3066763411df92631ee6afdcb19a08199b7a3ceb9483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378517324007786$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39094920$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yan, Chunyang</creatorcontrib><creatorcontrib>Nakajima, Mayuka</creatorcontrib><creatorcontrib>Ikeda-Imafuku, Mayumi</creatorcontrib><creatorcontrib>Yanagawa, Mayuko</creatorcontrib><creatorcontrib>Hayatsu, Manabu</creatorcontrib><creatorcontrib>Fukuta, Tatsuya</creatorcontrib><creatorcontrib>Shibata, Shinsuke</creatorcontrib><creatorcontrib>Mitragotri, Samir</creatorcontrib><creatorcontrib>Tabeta, Koichi</creatorcontrib><title>Choline and geranate ionic liquid for subgingival biofilm control</title><title>International journal of pharmaceutics</title><addtitle>Int J Pharm</addtitle><description>[Display omitted]
•Choline and geranate (CAGE) ionic liquid showed promise in treating subgingival infection.•Periodontal pathogens were killed by CAGE-induced cell membrane disruption.•CAGE overcame extracellular matrix, a physical barrier of biofilms that attenuates drug diffusion.•Subgingival biofilms were neutralized and eventually destroyed by CAGE treatment.
Periodontitis is a chronic inflammatory disease that causes destruction of the periodontium and eventual tooth loss. The priority in the periodontal treatment is to remove the subgingival biofilm. Chemical removal of biofilms using antimicrobial agents has been applied in clinical practice. However, their clinical effect is still limited because the agents must overcome biofilm’s significant drug tolerance, which is primarily caused by the extracellular matrix, a physical barrier that attenuates drug diffusion. This study aimed to study the use of ionic liquids (ILs), a new class of biocompatible materials, for controlling subgingival biofilms because of their excellent permeability. Choline and geranate (CAGE) IL was tested for its highly potent antiseptic behavior and permeability. Antibacterial tests revealed that the significant efficacy of CAGE against periodontopathic microorganisms was derived from their ability to destroy cell membrane, as demonstrated by membrane permeability assay and transmission electron microscopy imaging. Antibiofilm tests using two pathogenic biofilm models revealed that CAGE exerted efficacy against the biofilm-embedded bacteria, conspicuously neutralized the biofilms, and eventually destroyed the biofilm structure. Furthermore, the penetration of CAGE into the biofilm was visually confirmed using confocal laser scanning microscopy. This study highlighted the potential of CAGE as a powerful antibiofilm therapeutic.</description><subject>Biocompatible materials</subject><subject>Drug tolerance</subject><subject>Extracellular matrix</subject><subject>Ionic liquid</subject><subject>Periodontal pocket</subject><subject>Permeability</subject><issn>0378-5173</issn><issn>1873-3476</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqFkD1PwzAURS0EoqXwE0AZWVLs2HHiCVUVX1IlFpgtx35uHSVxaydI_HtSpbAyveXce_UOQrcELwkm_KFeunq_U6FdZjhjS5KxnLEzNCdlQVPKCn6O5pgWZZqTgs7QVYw1xphnhF6iGRVYMJHhOVqtd75xHSSqM8kWgupUD4nzndNJ4w6DM4n1IYlDtXXd1n2pJqmct65pE-27PvjmGl1Y1US4Od0F-nx--li_ppv3l7f1apPqTOA-La0yyuLSAjYiVywvmVEUc15wyggxVmScEgCurNEVEQqXRIiqUFRDJVhJF-h-6t0Hfxgg9rJ1UUPTqA78ECXFZZFzklM2ovmE6uBjDGDlPrhWhW9JsDzak7U82ZNHe3KyN-buThND1YL5S_3qGoHHCYDx0S8HQUbtoNNgXADdS-PdPxM_kXeDOg</recordid><startdate>20240905</startdate><enddate>20240905</enddate><creator>Yan, Chunyang</creator><creator>Nakajima, Mayuka</creator><creator>Ikeda-Imafuku, Mayumi</creator><creator>Yanagawa, Mayuko</creator><creator>Hayatsu, Manabu</creator><creator>Fukuta, Tatsuya</creator><creator>Shibata, Shinsuke</creator><creator>Mitragotri, Samir</creator><creator>Tabeta, Koichi</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20240905</creationdate><title>Choline and geranate ionic liquid for subgingival biofilm control</title><author>Yan, Chunyang ; Nakajima, Mayuka ; Ikeda-Imafuku, Mayumi ; Yanagawa, Mayuko ; Hayatsu, Manabu ; Fukuta, Tatsuya ; Shibata, Shinsuke ; Mitragotri, Samir ; Tabeta, Koichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c290t-8fadaf08fe0d95a4584da3066763411df92631ee6afdcb19a08199b7a3ceb9483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Biocompatible materials</topic><topic>Drug tolerance</topic><topic>Extracellular matrix</topic><topic>Ionic liquid</topic><topic>Periodontal pocket</topic><topic>Permeability</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yan, Chunyang</creatorcontrib><creatorcontrib>Nakajima, Mayuka</creatorcontrib><creatorcontrib>Ikeda-Imafuku, Mayumi</creatorcontrib><creatorcontrib>Yanagawa, Mayuko</creatorcontrib><creatorcontrib>Hayatsu, Manabu</creatorcontrib><creatorcontrib>Fukuta, Tatsuya</creatorcontrib><creatorcontrib>Shibata, Shinsuke</creatorcontrib><creatorcontrib>Mitragotri, Samir</creatorcontrib><creatorcontrib>Tabeta, Koichi</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yan, Chunyang</au><au>Nakajima, Mayuka</au><au>Ikeda-Imafuku, Mayumi</au><au>Yanagawa, Mayuko</au><au>Hayatsu, Manabu</au><au>Fukuta, Tatsuya</au><au>Shibata, Shinsuke</au><au>Mitragotri, Samir</au><au>Tabeta, Koichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Choline and geranate ionic liquid for subgingival biofilm control</atitle><jtitle>International journal of pharmaceutics</jtitle><addtitle>Int J Pharm</addtitle><date>2024-09-05</date><risdate>2024</risdate><volume>662</volume><spage>124544</spage><pages>124544-</pages><artnum>124544</artnum><issn>0378-5173</issn><issn>1873-3476</issn><eissn>1873-3476</eissn><abstract>[Display omitted]
•Choline and geranate (CAGE) ionic liquid showed promise in treating subgingival infection.•Periodontal pathogens were killed by CAGE-induced cell membrane disruption.•CAGE overcame extracellular matrix, a physical barrier of biofilms that attenuates drug diffusion.•Subgingival biofilms were neutralized and eventually destroyed by CAGE treatment.
Periodontitis is a chronic inflammatory disease that causes destruction of the periodontium and eventual tooth loss. The priority in the periodontal treatment is to remove the subgingival biofilm. Chemical removal of biofilms using antimicrobial agents has been applied in clinical practice. However, their clinical effect is still limited because the agents must overcome biofilm’s significant drug tolerance, which is primarily caused by the extracellular matrix, a physical barrier that attenuates drug diffusion. This study aimed to study the use of ionic liquids (ILs), a new class of biocompatible materials, for controlling subgingival biofilms because of their excellent permeability. Choline and geranate (CAGE) IL was tested for its highly potent antiseptic behavior and permeability. Antibacterial tests revealed that the significant efficacy of CAGE against periodontopathic microorganisms was derived from their ability to destroy cell membrane, as demonstrated by membrane permeability assay and transmission electron microscopy imaging. Antibiofilm tests using two pathogenic biofilm models revealed that CAGE exerted efficacy against the biofilm-embedded bacteria, conspicuously neutralized the biofilms, and eventually destroyed the biofilm structure. Furthermore, the penetration of CAGE into the biofilm was visually confirmed using confocal laser scanning microscopy. This study highlighted the potential of CAGE as a powerful antibiofilm therapeutic.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>39094920</pmid><doi>10.1016/j.ijpharm.2024.124544</doi><oa>free_for_read</oa></addata></record> |
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subjects | Biocompatible materials Drug tolerance Extracellular matrix Ionic liquid Periodontal pocket Permeability |
title | Choline and geranate ionic liquid for subgingival biofilm control |
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