Fuente: PubMed "swarm" Int J Pharm. 2026 May 28:127019. doi: 10.1016/j.ijpharm.2026.127019. Online ahead of print.ABSTRACTBACKGROUND: The alarming rise of multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa) demands anti-infective strategies beyond conventional antibiotics. Quorum sensing inhibitors (QSIs) represent a promising anti-virulence approach, yet their clinical translation is often hindered by poor solubility and formulation challenges. Nanostructured lipid carriers (NLCs) represent a multifunctional platform to overcome these barriers.OBJECTIVE: Herein, we developed a squalene-based NLC encapsulating a rationally designed QS inhibitor (Y0-C10-HSL) and systematically evaluated its anti-virulence efficacy against P. aeruginosa using both in vitro and in vivo models.METHODS: Y0-C10-HSL@NLCs were prepared via high-shear homogenization coupled with probe sonication and optimized using response surface methodology based on solid-to-liquid lipid ratio, lipid-to-drug ratio, and stirring time. The optimized formulation was characterized for particle size, zeta potential, morphology, and in vitro drug release. Its anti-virulence potential was assessed through inhibition of biofilm formation, disruption of pre-established biofilms, suppression of virulence factors (pyocyanin, rhamnolipids, proteases), and impairment of bacterial motility. Therapeutic efficacy was further validated in a Caenorhabditis elegans infection model.RESULTS: The optimized formulation (solid-to-liquid lipid ratio 4:1, lipid-to-drug ratio 16:1, stirring time 26 min) exhibited an encapsulation efficiency of 61.58% and a 24 h cumulative release of 62.60%. The nanoparticles had a mean diameter of 385.90 ± 7.50 nm, a zeta potential of -22.1 ± 0.9 mV, and a PDI of 0.217. At 400 μg/mL, Y0-C10-HSL@NLCs inhibited biofilm formation by 51.99% and disrupted pre-formed biofilms by 65.42% (p < 0.001). The formulation also dose-dependently suppressed pyocyanin, rhamnolipids, and protease production, and impaired swarming, swimming, and twitching motility. In C. elegans, the formulation was non-toxic and significantly enhanced the survival of infected worms (e.g., 88.6% survival at 24 h vs. 51.1% in untreated controls), confirming its in vivo protective efficacy.CONCLUSION: Collectively, these findings establish Y0-C10-HSL@NLCs as a potent and versatile anti-virulence platform that effectively overcomes the delivery limitations of synthetic QSIs and combats P. aeruginosa infections through multi-targeted disruption of both biofilm formation and virulence.PMID:42214707 | DOI:10.1016/j.ijpharm.2026.127019