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

被引：47

作者：

Ho, Duy-Khiet ^{[1
,5
,6
]}

Murgia, Xabier ^{[1
,5
,7
]}

De Rossi, Chiara ^{[1
]}

Christmann, Rebekka ^{[1
,5
]}

Huefner de Mello Martins, Antonio G. ^{[1
]}

Koch, Marcus ^{[2
]}

Andreas, Anastasia ^{[1
,4
]}

Herrmann, Jennifer ^{[1
,4
]}

Mueller, Rolf ^{[1
,4
,5
]}

Empting, Martin ^{[1
,4
,5
]}

Hartmann, Rolf W. ^{[1
,4
,5
]}

Desmaele, Didier ^{[3
]}

Loretz, Brigitta ^{[1
]}

Couvreur, Patrick ^{[3
]}

Lehr, Claus-Michael ^{[1
,5
]}

机构：

[1] Helmholtz Ctr Infect Res, Helmholtz Inst Pharmaceut Res Saarland, Saarbrucken 66123, Germany

[2] INM Leibniz Inst New Mat, Saarbrucken 66123, Germany

[3] Univ Paris Saclay, Fac Pharm, Inst Galien Paris Sud, UMR CNRS 8612, Chatenay Malabry 92296, France

[4] German Ctr Infect Res DZIF, Partner Site Hannover Braunschweig, Saarbrucken 66123, Germany

[5] Saarland Univ, Dept Pharm, Saarbrucken 66123, Germany

[6] Univ Washington, Sch Med, Dept Bioengn, Seattle, WA 98195 USA

[7] Kusudama Therapeut, Parque Cient & Tecnol Gipuzkoa, Donostia San Sebastian 20014, Spain

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2020年 / 59卷 / 26期

基金：

欧盟地平线“2020”;

关键词：

biofilms; drug delivery; Pseudomonas aeruginosa; quorum sensing inhibitors; tobramycin; PSEUDOMONAS-AERUGINOSA; BACTERIAL BIOFILMS; ANTIBIOTICS; RESISTANCE;

D O I：

10.1002/anie.202001407

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：10292 / 10296

页数：5

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