title: A Topical Hydrogel with Deferiprone and Gallium-Protoporphyrin Targets Bacterial Iron Metabolism and Has Antibiofilm Activity.
abstract: Many infectious diseases are associated with multidrug-resistant (MDR) bacteria residing in biofilms that require high antibiotic concentrations. While oral drug delivery is frequently ineffective, topical treatments have the potential to deliver higher drug concentrations to the infection site while reducing systemic side effects. This study determined the antibiofilm activity of a surgical wound gel loaded with the iron chelator deferiprone (Def) and the heme analogue gallium-protoporphyrin (GaPP), alone and in combination with ciprofloxacin. Activity against MDRStaphylococcus aureus,Staphylococcus epidermidis,Pseudomonas aeruginosa, andAcinetobacter johnsoniibiofilms was assessed in the colony biofilm and artificial wound model by enumeration of CFU and correlative light/electron microscopy. WhileStaphylococcusbiofilms were equally susceptible to GaPP and Def-GaPP gels (log10reduction of 3.8 and 3.7, respectively), the Def-GaPP combination was crucial for significant activity againstP. aeruginosabiofilms (log10reduction of 1.3 for GaPP and 3.3 for Def-GaPP). When Def-GaPP gel was combined with ciprofloxacin, the efficacy exceeded the activity of the individual compounds. Def-GaPP delivered in a surgical wound gel showed significant antibiofilm activity against different MDR strains and could enhance the gel's wound-healing properties. Moreover, Def-GaPP indicated a potentiation of ciprofloxacin. This antibiofilm strategy has potential for clinical utilization as a therapy for topical biofilm-related infections.
authors.affiliation: Department of Surgery, Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Katharina
authors.identifier: 0000-0003-2979-8215
authors.initials: K
authors.lastname: Richter
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.|Adelaide Biofilm Test Facility, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Nicky
authors.identifier: 0000-0001-8920-1391
authors.initials: N
authors.lastname: Thomas
authors.affiliation: Laboratory of Pharmaceutical Microbiology, Ghent University, Ghent, Belgium.
authors.forename: Jolien
authors.initials: J
authors.lastname: Claeys
authors.affiliation: Department of Surgery, Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: McGuane
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Adelaide, South Australia, Australia.
authors.forename: Clive A
authors.initials: CA
authors.lastname: Prestidge
authors.affiliation: Laboratory of Pharmaceutical Microbiology, Ghent University, Ghent, Belgium.
authors.forename: Tom
authors.identifier: 0000-0002-6407-0601
authors.initials: T
authors.lastname: Coenye
authors.affiliation: Department of Surgery, Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Peter-John
authors.initials: PJ
authors.lastname: Wormald
authors.affiliation: Department of Surgery, Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, The University of Adelaide, Adelaide, South Australia, Australia sarah.vreugde@adelaide.edu.au.
authors.forename: Sarah
authors.initials: S
authors.lastname: Vreugde
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D000077543:Deferiprone; D005708:Gallium / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011524:Protoporphyrins / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011728:Pyridones / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D011524:Protoporphyrins; D011728:Pyridones; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D000077543:Deferiprone; D005708:Gallium
keywords: antimicrobial combinations; biofilms; drug delivery; iron metabolism