Open Access

Duy-Khiet Ho, Xabier Murgia, Chiara De Rossi, Rebekka Christmann, Antonio G. Hüfner de Mello Martins, Marcus Koch, Anastasia Andreas, Jennifer Herrmann, Rolf Müller, Martin Empting, Rolf W. Hartmann, Didier Desmaele, Brigitta Loretz, Patrick Couvreur, Claus-Michael Lehr

• 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.