Tobramycin Liquid Crystal Nanoparticles Eradicate Cystic Fibrosis-Related Pseudomonas aeruginosa Biofilms.

Autor: Thorn CR; Clinical and Health Science, University of South Australia, North Tce, Adelaide, SA, 5000, Australia.; The Basil Hetzel Institute for Translational Health Research, Woodville, SA, 5011, Australia.; ARC Centre for Excellence in Bio-Nano Science and Technology, Australia.; Adelaide Biofilm Test Facility, Cancer Research Institute, University of South Australia, North Tce, Adelaide, SA, 5000, Australia., Carvalho-Wodarz CS; Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), 66123, Saarbrücken, Germany., Horstmann JC; Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), 66123, Saarbrücken, Germany.; Department of Pharmacy, Saarland University, 66123, Saarbrücken, Germany., Lehr CM; Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), 66123, Saarbrücken, Germany.; Department of Pharmacy, Saarland University, 66123, Saarbrücken, Germany., Prestidge CA; Clinical and Health Science, University of South Australia, North Tce, Adelaide, SA, 5000, Australia.; ARC Centre for Excellence in Bio-Nano Science and Technology, Australia., Thomas N; Clinical and Health Science, University of South Australia, North Tce, Adelaide, SA, 5000, Australia.; The Basil Hetzel Institute for Translational Health Research, Woodville, SA, 5011, Australia.; ARC Centre for Excellence in Bio-Nano Science and Technology, Australia.; Adelaide Biofilm Test Facility, Cancer Research Institute, University of South Australia, North Tce, Adelaide, SA, 5000, Australia.
Jazyk: angličtina
Zdroj: Small (Weinheim an der Bergstrasse, Germany) [Small] 2021 Jun; Vol. 17 (24), pp. e2100531. Date of Electronic Publication: 2021 May 12.
DOI: 10.1002/smll.202100531
Abstrakt: Pseudomonas aeruginosa biofilms cause persistent and chronic infections, most known clinically in cystic fibrosis (CF). Tobramycin (TOB) is a standard anti-pseudomonal antibiotic; however, in biofilm infections, its efficacy severely decreases due to limited permeability across the biofilm matrix. Herewith, a biomimetic, nanostructured, lipid liquid crystal nanoparticle-(LCNP)-formulation is discovered to significantly enhance the efficacy of TOB and eradicate P. aeruginosa biofilm infections. Using an advanced, biologically-relevant co-culture model of human CF bronchial epithelial cells infected with P. aeruginosa biofilms at an air-liquid interface, nebulized TOB-LCNPs completely eradicated 1 × 10 9 CFU mL -1 of P. aeruginosa after two doses, a 100-fold improvement over the unformulated antibiotic. The enhanced activity of TOB is not observed with a liposomal formulation of TOB or with ciprofloxacin, an antibiotic that readily penetrates biofilms. It is demonstrated that the unique nanostructure of the LCNPs drives the enhanced penetration of TOB across the biofilm barrier, but not through the healthy lung epithelium barrier, significantly increasing the available antibiotic concentration at the site of infection. The LCNPs are an innovative strategy to improve the performance of TOB as a directed pulmonary therapy, enabling the administration of lower doses, reducing the toxicity, and amplifying the anti-biofilm activity of the anti-pseudomonal antibiotic.
(© 2021 Wiley-VCH GmbH.)
Databáze: MEDLINE
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