Kasza, K. orcid.org/0000-0001-5881-1744, Soukarieh, F. orcid.org/0000-0002-6730-2543, Romero, M. orcid.org/0000-0001-6902-6776 et al. (4 more authors) (2024) Triblock copolymer micelles enhance solubility, permeability and activity of a quorum sensing inhibitor against Pseudomonas aeruginosa biofilms. RSC Applied Polymers, 2 (3). pp. 444-455. ISSN 2755-371X
Abstract
Antimicrobial resistance is a threat to public health for which new treatments are urgently required. The capability of bacteria to form biofilms is of particular concern as it enables high bacterial tolerance to conventional therapies by reducing drug diffusion through the dense, exopolymeric biofilm matrix and the upregulation of antimicrobial resistance machinery. Quorum sensing (QS), a process where bacteria use diffusible chemical signals to coordinate group behaviour, has been shown to be closely interconnected with biofilm formation and bacterial virulence in many top priority pathogens including Pseudomonas aeruginosa. Inhibition of QS pathways therefore pose an attractive target for new therapeutics. We have recently reported a new series of pqs quorum sensing inhibitors (QSIs) that serve as potentiators for antibiotics in P. aeruginosa infections. The impact on biofilms of some reported QSIs was however hindered by their poor penetration through the bacterial biofilm, limiting the potential for clinical translation. In this study we developed a series of poly(β-amino ester) (PBAE) triblock copolymers and evaluated their ability to form micelles, encapsulate a QSI and enhance subsequent delivery to P. aeruginosa biofilms. We observed that the QSI could be released from polymer micelles, perturbing the pqs pathway in planktonic P. aeruginosa. In addition, one of the prepared polymer variants increased the QSIs efficacy, leading to an enhanced potentiation of ciprofloxacin (CIP) action and therefore improved reduction in biofilm viability, compared to the non-encapsulated QSI. Thus, we demonstrate QSI encapsulation in polymeric particles can enhance its efficacy through improved biofilm penetration.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The author(s). This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (http://creativecommons.org/licenses/by/3.0/). |
Keywords: | Microbiology; Medical Microbiology; Biomedical and Clinical Sciences; Biological Sciences; Infectious Diseases; Lung; Emerging Infectious Diseases; Biodefense; Rare Diseases; Cystic Fibrosis; Antimicrobial Resistance; Pharmaceuticals; Factors relating to the physical environment; Infection |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Health Sciences School (Sheffield) |
Funding Information: | Funder Grant number BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/R012415/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 29 Jan 2025 15:43 |
Last Modified: | 29 Jan 2025 15:43 |
Status: | Published |
Publisher: | Royal Society of Chemistry (RSC) |
Refereed: | Yes |
Identification Number: | 10.1039/d3lp00208j |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:222439 |