A Potential Quorum-Sensing Inhibitor for Bronchiectasis Therapy: Quercetin–Chitosan Nanoparticle Complex Exhibiting Superior Inhibition of Biofilm Formation and Swimming Motility of <i>Pseudomonas aeruginosa</i> to the Native Quercetin
Quercetin (QUE)—a plant-derived flavonoid, is recently established as an effective quorum sensing (QS) inhibiting agent in <i>Pseudomonas aeruginosa</i>—the main bacterial pathogen in bronchiectasis lungs. Successful clinical application of QUE, however, is hindered by its low solubility...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/1541 |
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| author | The-Thien Tran Kunn Hadinoto |
| author_facet | The-Thien Tran Kunn Hadinoto |
| author_sort | The-Thien Tran |
| collection | DOAJ |
| description | Quercetin (QUE)—a plant-derived flavonoid, is recently established as an effective quorum sensing (QS) inhibiting agent in <i>Pseudomonas aeruginosa</i>—the main bacterial pathogen in bronchiectasis lungs. Successful clinical application of QUE, however, is hindered by its low solubility in physiological fluids. Herein we developed a solubility enhancement strategy of QUE in the form of a stable amorphous nanoparticle complex (nanoplex) of QUE and chitosan (CHI), which was prepared by electrostatically driven complexation between ionized QUE molecules and oppositely charged CHI. At its optimal preparation condition, the QUE–CHI nanoplex exhibited a size of roughly 150 nm with a 25% QUE payload and 60% complexation efficiency. The complexation with CHI had no adverse effect on the antibacterial and anticancer activities of QUE, signifying the preservation of QUE’s bioactivities in the nanoplex. Compared to the native QUE, the QUE–CHI nanoplex exhibited superior QS inhibition in suppressing the QS-regulated swimming motility and biofilm formation of <i>P. aeruginosa</i>, but not in suppressing the virulence factor production. The superior inhibitions of the biofilm formation and swimming motility afforded by the nanoplex were attributed to (1) its higher kinetic solubility (5-times higher) that led to higher QUE exposures, and (2) the synergistic QS inhibition attributed to its CHI fraction. |
| first_indexed | 2024-03-09T05:50:09Z |
| format | Article |
| id | doaj.art-5e255b08baac4ce8b6d096716491da51 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:50:09Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5e255b08baac4ce8b6d096716491da512023-12-03T12:17:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224154110.3390/ijms22041541A Potential Quorum-Sensing Inhibitor for Bronchiectasis Therapy: Quercetin–Chitosan Nanoparticle Complex Exhibiting Superior Inhibition of Biofilm Formation and Swimming Motility of <i>Pseudomonas aeruginosa</i> to the Native QuercetinThe-Thien Tran0Kunn Hadinoto1School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459, SingaporeSchool of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459, SingaporeQuercetin (QUE)—a plant-derived flavonoid, is recently established as an effective quorum sensing (QS) inhibiting agent in <i>Pseudomonas aeruginosa</i>—the main bacterial pathogen in bronchiectasis lungs. Successful clinical application of QUE, however, is hindered by its low solubility in physiological fluids. Herein we developed a solubility enhancement strategy of QUE in the form of a stable amorphous nanoparticle complex (nanoplex) of QUE and chitosan (CHI), which was prepared by electrostatically driven complexation between ionized QUE molecules and oppositely charged CHI. At its optimal preparation condition, the QUE–CHI nanoplex exhibited a size of roughly 150 nm with a 25% QUE payload and 60% complexation efficiency. The complexation with CHI had no adverse effect on the antibacterial and anticancer activities of QUE, signifying the preservation of QUE’s bioactivities in the nanoplex. Compared to the native QUE, the QUE–CHI nanoplex exhibited superior QS inhibition in suppressing the QS-regulated swimming motility and biofilm formation of <i>P. aeruginosa</i>, but not in suppressing the virulence factor production. The superior inhibitions of the biofilm formation and swimming motility afforded by the nanoplex were attributed to (1) its higher kinetic solubility (5-times higher) that led to higher QUE exposures, and (2) the synergistic QS inhibition attributed to its CHI fraction.https://www.mdpi.com/1422-0067/22/4/1541quercetin nanoparticlesdrug-polyelectrolyte complexationamorphous drugsquorum sensingbronchiectasis therapy<i>Pseudomonas</i> biofilm |
| spellingShingle | The-Thien Tran Kunn Hadinoto A Potential Quorum-Sensing Inhibitor for Bronchiectasis Therapy: Quercetin–Chitosan Nanoparticle Complex Exhibiting Superior Inhibition of Biofilm Formation and Swimming Motility of <i>Pseudomonas aeruginosa</i> to the Native Quercetin International Journal of Molecular Sciences quercetin nanoparticles drug-polyelectrolyte complexation amorphous drugs quorum sensing bronchiectasis therapy <i>Pseudomonas</i> biofilm |
| title | A Potential Quorum-Sensing Inhibitor for Bronchiectasis Therapy: Quercetin–Chitosan Nanoparticle Complex Exhibiting Superior Inhibition of Biofilm Formation and Swimming Motility of <i>Pseudomonas aeruginosa</i> to the Native Quercetin |
| title_full | A Potential Quorum-Sensing Inhibitor for Bronchiectasis Therapy: Quercetin–Chitosan Nanoparticle Complex Exhibiting Superior Inhibition of Biofilm Formation and Swimming Motility of <i>Pseudomonas aeruginosa</i> to the Native Quercetin |
| title_fullStr | A Potential Quorum-Sensing Inhibitor for Bronchiectasis Therapy: Quercetin–Chitosan Nanoparticle Complex Exhibiting Superior Inhibition of Biofilm Formation and Swimming Motility of <i>Pseudomonas aeruginosa</i> to the Native Quercetin |
| title_full_unstemmed | A Potential Quorum-Sensing Inhibitor for Bronchiectasis Therapy: Quercetin–Chitosan Nanoparticle Complex Exhibiting Superior Inhibition of Biofilm Formation and Swimming Motility of <i>Pseudomonas aeruginosa</i> to the Native Quercetin |
| title_short | A Potential Quorum-Sensing Inhibitor for Bronchiectasis Therapy: Quercetin–Chitosan Nanoparticle Complex Exhibiting Superior Inhibition of Biofilm Formation and Swimming Motility of <i>Pseudomonas aeruginosa</i> to the Native Quercetin |
| title_sort | potential quorum sensing inhibitor for bronchiectasis therapy quercetin chitosan nanoparticle complex exhibiting superior inhibition of biofilm formation and swimming motility of i pseudomonas aeruginosa i to the native quercetin |
| topic | quercetin nanoparticles drug-polyelectrolyte complexation amorphous drugs quorum sensing bronchiectasis therapy <i>Pseudomonas</i> biofilm |
| url | https://www.mdpi.com/1422-0067/22/4/1541 |
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