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

## TL;DR

Researchers developed polymer micelles to improve the delivery and effectiveness of a quorum sensing inhibitor against Pseudomonas aeruginosa biofilms when used with ciprofloxacin.

## Contribution

A new polymeric delivery system was developed to enhance the biofilm penetration and efficacy of quorum sensing inhibitors.

## Key findings

- Polymer micelles enabled the release of quorum sensing inhibitors and disrupted the pqs pathway in Pseudomonas aeruginosa.
- One polymer variant improved the efficacy of quorum sensing inhibitors when combined with ciprofloxacin, reducing biofilm viability.
- Encapsulation in polymeric particles enhanced the potency of quorum sensing inhibitors through better biofilm penetration.

## 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.

Combination therapies offer potential solutions to the growing threats of antimicrobial resistance. We describe polymer delivery materials for Quorum Sensing Inhibitors used in combination with ciprofloxacin to enhance potency in bacterial biofilms.