Tobramycin Liquid Crystal Nanoparticles Eradicate Cystic Fibrosis‐Related Pseudomonas aeruginosa Biofilms. Issue 24 (12th May 2021)

• Record Type: Journal Article
• Authors: Thorn, Chelsea R.; Carvalho‐Wodarz, Cristiane de Souza; Horstmann, Justus C.; Lehr, Claus‐Michael; Prestidge, Clive A.; Thomas, Nicky
• Is Part Of: Small. Volume 17:Issue 24(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-05-12
• Subjects: antimicrobials -- biofilms -- cystic fibrosis -- liquid crystals -- lung infection co‐cultures -- pulmonary drug delivery; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202100531
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: 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. Abstract : Formulation of tobramycin lipid liquid crystal nanoparticles eradicates highly tolerant Pseudomonas aeruginosa biofilms infection in bronchial epithelium. The unique lipid liquid crystal nanostructures form a patch over the biofilm, driving increased penetration, and concentration of the antibiotic to the site of bacteria while not surpassing the epithelium.