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Squalenyl Hydrogen Sulfate Nanoparticles for Simultaneous Delivery of Tobramycin and an Alkylquinolone Quorum Sensing Inhibitor Enable the Eradication of P. aeruginosa Biofilm Infections

  • Abstract Elimination of pulmonary Pseudomonas aeruginosa (PA) infections is challenging to accomplish with antibiotic therapies, mainly due to resistance mechanisms. Quorum sensing inhibitors (QSIs) interfering with biofilm formation can thus complement antibiotics. For simultaneous and improved delivery of both active agents to the infection sites, self-assembling nanoparticles of a newly synthesized squalenyl hydrogen sulfate (SqNPs) were prepared. These nanocarriers allowed for remarkably high loading capacities of hydrophilic antibiotic tobramycin (Tob) and a novel lipophilic QSI at 30 % and circa 10 %, respectively. The drug-loaded SqNPs showed improved biofilm penetration and enhanced efficacy in relevant biological barriers (mucin/human tracheal mucus, biofilm), leading to complete eradication of PA biofilms at circa 16-fold lower Tob concentration than Tob alone. This study offers a viable therapy optimization and invigorates the research and development of QSIs for clinical use.

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Document Type:Article
Author:Duy-Khiet HoORCiD, Xabier MurgiaORCiD, Chiara De Rossi, Rebekka ChristmannORCiD, Antonio G. Hüfner de Mello Martins, Marcus Koch, Anastasia Andreas, Jennifer HerrmannORCiD, Rolf MüllerORCiD, Martin EmptingORCiD, Rolf W. Hartmann, Didier Desmaele, Brigitta LoretzORCiD, Patrick Couvreur, Claus-Michael LehrORCiD
Parent Title (English):Angewandte Chemie International Edition
First Page:10292
Last Page:10296
Year of first Publication:2020
Release Date:2022/11/18
Impact:12.959 (2020)
Funding Information:H2020 Marie Sk łodowska-Curie Actions (642028) Deutsches Zentrum für Infektionsforschung (TTU09.908)
Groups:Physikalische Analytik
Open Access:Open Access
Signature:INM 2020/050
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International