Issue 3, 2024

Triblock copolymer micelles enhance solubility, permeability and activity of a quorum sensing inhibitor against Pseudomonas aeruginosa biofilms

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.

Graphical abstract: Triblock copolymer micelles enhance solubility, permeability and activity of a quorum sensing inhibitor against Pseudomonas aeruginosa biofilms

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Article information

Article type
Paper
Submitted
17 Oct 2023
Accepted
26 Feb 2024
First published
27 Feb 2024
This article is Open Access
Creative Commons BY license

RSC Appl. Polym., 2024,2, 444-455

Triblock copolymer micelles enhance solubility, permeability and activity of a quorum sensing inhibitor against Pseudomonas aeruginosa biofilms

K. Kasza, F. Soukarieh, M. Romero, K. R. Hardie, P. Gurnani, M. Cámara and C. Alexander, RSC Appl. Polym., 2024, 2, 444 DOI: 10.1039/D3LP00208J

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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