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

  1. Kasza, Karolina 13
  2. Soukarieh, Fadi 1
  3. Romero, Manuel 145
  4. Hardie, Kim R. 1
  5. Gurnani, Pratik 2
  6. Cámara, Miguel 1
  7. Alexander, Cameron 3
  1. 1 National Biofilms Innovation Centre, School of Life Sciences, Biodiscovery Institute, University Park, University of Nottingham, Nottingham NG7 2RD, UK
  2. 2 UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK
  3. 3 Division of Molecular Therapeutics and Formulation, School of Pharmacy, University of Nottingham, NG7 2RD, UK
  4. 4 Department of Microbiology and Parasitology, Faculty of Biology-CIBUS, Universidade de Santiago de Compostela, Santiago de Compostela, 15782, Spain
  5. 5 Aquatic One Health Research Center (ARCUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15782, Spain
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Revista:
RSC Applied Polymers

ISSN: 2755-371X

Ano de publicación: 2024

Tipo: Artigo

DOI: 10.1039/D3LP00208J GOOGLE SCHOLAR lock_openAcceso aberto editor

Outras publicacións en: RSC Applied Polymers

Resumo

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.

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