Issue 27, 2025, Issue in Progress

Development and evaluation of new nanoformulated thiolactone derivatives for enhanced disruption of pseudomonal biofilms

Abstract

Pseudomonas aeruginosa (P. aeruginosa) is a formidable, antibiotic-resistant pathogen responsible for severe infections, particularly due to its ability to form protective biofilms mediated by the quorum sensing (QS) system, a cell-to-cell communication mechanism essential for biofilm formation and virulence. Herein, we developed a novel nanoformulation of thiolactone derivatives designed to target the QS system of P. aeruginosa. Specifically, chlorothiolactone (CTL) compounds (mCTL, 4a and pCTL, 4b) were encapsulated within biocompatible pluronic nanoparticles to enhance their delivery and efficacy. Our nanoformulation demonstrated efficient delivery of the designated molecules, leading to inhibition of the LasR receptor, a key regulator of QS, and subsequent disruption of biofilm formation. Our results revealed that the nanoparticle-formulated CTL derivatives exhibited superior activity in influencing the kinetics of P. aeruginosa biofilm and suppressing the virulence factors of P. aeruginosa, including pyocyanin and rhamnolipid production, compared to their free counterparts. Preliminary mechanistic studies indicated that the nanoformulation significantly reduced exopolysaccharide production, a critical component for biofilm integrity. Collectively, these findings underscore the potential of 4a-NPs and 4b-NPs as promising therapeutic candidates for combating P. aeruginosa infections by targeting its QS-mediated biofilm formation and virulence.

Graphical abstract: Development and evaluation of new nanoformulated thiolactone derivatives for enhanced disruption of pseudomonal biofilms

Supplementary files

Article information

Article type
Paper
Submitted
14 Mar 2025
Accepted
31 May 2025
First published
24 Jun 2025
This article is Open Access
Creative Commons BY license

RSC Adv., 2025,15, 21369-21380

Development and evaluation of new nanoformulated thiolactone derivatives for enhanced disruption of pseudomonal biofilms

M. K. Gaballah, S. A. Khalid, M. A. Seleem, A. K. A. Bass, I. M. El-Sherbiny and A. S. Mayhoub, RSC Adv., 2025, 15, 21369 DOI: 10.1039/D5RA01831E

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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