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.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Squalenyl Hydrogen Sulfate Nanoparticles for Simultaneous Delivery of Tobramycin and an Alkylquinolone Quorum Sensing Inhibitor Enable the Eradication of P. aeruginosa Biofilm Infections ; volume:59 ; number:26 ; year:2020 ; pages:10292-10296 ; extent:5
Angewandte Chemie / International edition. International edition ; 59, Heft 26 (2020), 10292-10296 (gesamt 5)

Urheber
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
Hartmann, Rolf W.
Desmaele, Didier
Loretz, Brigitta
Couvreur, Patrick
Lehr, Claus‐Michael

DOI
10.1002/anie.202001407
URN
urn:nbn:de:101:1-2022061212552419056536
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
07.08.2025, 11:03 MESZ

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Beteiligte

  • 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
  • Hartmann, Rolf W.
  • Desmaele, Didier
  • Loretz, Brigitta
  • Couvreur, Patrick
  • Lehr, Claus‐Michael

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