Tobramycin Liquid Crystal Nanoparticles Eradicate Cystic Fibrosis-Related Pseudomonas aeruginosa Biofilms.
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Authors
Thorn, Chelsea RCarvalho-Wodarz, Cristiane de Souza
Horstmann, Justus C
Lehr, Claus-Michael
Prestidge, Clive A
Thomas, Nicky
Issue Date
2021-05-12
Metadata
Show full item recordAbstract
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 × 109 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.Citation
Small. 2021 Jun;17(24):e2100531. doi: 10.1002/smll.202100531. Epub 2021 May 12.Affiliation
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.Publisher
Wiley-VCHPubMed ID
33978317Type
ArticleLanguage
enEISSN
1613-6829ae974a485f413a2113503eed53cd6c53
10.1002/smll.202100531
Scopus Count
The following license files are associated with this item:
- Creative Commons
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