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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.
Ho, Duy-Khiet Murgia, Xabier de Rossi, Chiara Christmann, Rebekka Hüfner de Mello Martins, Antonio G Koch, Marcus Andreas, Anastasia Herrmann, Jennifer Müller, Rolf Empting, Martin
Ho, Duy-Khiet
Murgia, Xabier
de Rossi, Chiara
Christmann, Rebekka
Hüfner de Mello Martins, Antonio G
Koch, Marcus
Andreas, Anastasia
Herrmann, Jennifer
Müller, Rolf
Empting, Martin
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2020-04-03
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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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Angew Chem Int Ed Engl. 2020;10.1002/anie.202001407. doi:10.1002/anie.202001407.
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Article
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en
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1521-3773
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Attribution-NonCommercial-ShareAlike 4.0 International