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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
Author(s) -
Ho DuyKhiet,
Murgia Xabier,
De Rossi Chiara,
Christmann Rebekka,
Hüfner de Mello Martins Antonio G.,
Koch Marcus,
Andreas Anastasia,
Herrmann Jennifer,
Müller Rolf,
Empting Martin,
Hartmann Rolf W.,
Desmaele Didier,
Loretz Brigitta,
Couvreur Patrick,
Lehr ClausMichael
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202001407
Subject(s) - biofilm , tobramycin , pseudomonas aeruginosa , microbiology and biotechnology , quorum sensing , nanocarriers , antibiotics , chemistry , drug delivery , bacteria , biology , organic chemistry , genetics , gentamicin
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.