title: Investigation of the enhanced antimicrobial activity of combination dry powder inhaler formulations of lactoferrin.
abstract: The airways of most people with cystic fibrosis are colonized with biofilms of the Gram-negative, opportunistic pathogen Pseudomonas aeruginosa. Delivery of antibiotics directly to the lung in the form of dry powder aerosols offers the potential to achieve high local concentrations directly to the biofilms. Unfortunately, current aerosolised antibiotic regimes are unable to efficiently eradicate these biofilms from the airways. We investigated the ability of the innate antimicrobial, lactoferrin, to enhance the activity of two aminoglycoside antibiotics (tobramycin and gentamicin) against biofilms of P. aeruginosa strain PAO1. Biofilms were prepared in 96 well polystyrene plates. Combinations of the antibiotics and various lactoferrin preparations were spray dried. The bacterial cell viability of the various spray dried combinations was determined. Iron-free lactoferrin (apo lactoferrin) induced a 3-log reduction in the killing of planktonic cell by the aminoglycoside antibiotics (p<0.01) and also reduced both the formation and persistence of P. aeruginosa biofilms (p<0.01). Combinations of lactoferrin and an aminoglycoside displays potential as an effective new therapeutic strategy in the treatment of P. aeruginosa biofilms infections such as those typical of the CF lungs.
authors.affiliation: Cell and Tissue Biomedical Research Group, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK.
authors.forename: Lindsay J
authors.initials: LJ
authors.lastname: Marshall
authors.affiliation: Cell and Tissue Biomedical Research Group, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK.
authors.forename: Wilson
authors.initials: W
authors.lastname: Oguejiofor
authors.affiliation: Pharmaceutical Surface Science Research Group, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Price
authors.affiliation: Pharmaceutical Surface Science Research Group, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK. Electronic address: j.shur@bath.ac.uk.
authors.forename: Jagdeep
authors.initials: J
authors.lastname: Shur
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D001059:Apoproteins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004339:Drug Compounding; D004357:Drug Synergism; D005839:Gentamicins / Q000494:pharmacology*; D007781:Lactoferrin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D011208:Powders; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D014031:Tobramycin / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D001059:Apoproteins; D005839:Gentamicins; D011208:Powders; C039223:apolactoferrin; D007781:Lactoferrin; D014031:Tobramycin
keywords: Antimicrobial protein; Biofilms; Cystic fibrosis; Dry powder inhalers; Pseudomonas aeruginosa; Spray drying