title: Controlled delivery of antimicrobial gallium ions from phosphate-based glasses.
abstract: Gallium-doped phosphate-based glasses (PBGs) have been recently shown to have antibacterial activity. However, the delivery of gallium ions from these glasses can be improved by altering the calcium ion concentration to control the degradation rate of the glasses. In the present study, the effect of increasing calcium content in novel gallium (Ga2O3)-doped PBGs on the susceptibility of Pseudomonas aeruginosa is examined. The lack of new antibiotics in development makes gallium-doped PBG potentially a highly promising new therapeutic agent. The results show that an increase in calcium content (14, 15 and 16 mol.% CaO) cause a decrease in degradation rate (17.6, 13.5 and 7.3 microg mm(-2) h(-1)), gallium ion release and antimicrobial activity against planktonic P. aeruginosa. The most potent glass composition (containing 14 mol.% CaO) was then evaluated for its ability to prevent the growth of biofilms of P. aeruginosa. Gallium release was found to reduce biofilm growth of P. aeruginosa with a maximum effect (0.86 log(10) CFU reduction compared to Ga2O3-free glasses) after 48 h. Analysis of the biofilms by confocal microscopy confirmed the anti-biofilm effect of these glasses as it showed both viable and non-viable bacteria on the glass surface. Results of the solubility and ion release studies show that this glass system is suitable for controlled delivery of Ga3+. 71Ga NMR and Ga K-edge XANES measurements indicate that the gallium is octahedrally coordinated by oxygen atoms in all samples. The results presented here suggest that PBGs may be useful in controlled drug delivery applications, to deliver gallium ions in order to prevent infections due to P. aeruginosa biofilms.
authors.affiliation: Division of Biomaterials and Tissue Engineering, University College London, Eastman Dental Institute, 256 Gray's Inn Road, London, UK.
authors.forename: S P
authors.initials: SP
authors.lastname: Valappil
authors.forename: D
authors.initials: D
authors.lastname: Ready
authors.forename: E A
authors.initials: EA
authors.lastname: Abou Neel
authors.forename: D M
authors.initials: DM
authors.lastname: Pickup
authors.forename: L A
authors.initials: LA
authors.lastname: O'Dell
authors.forename: W
authors.initials: W
authors.lastname: Chrzanowski
authors.forename: J
authors.initials: J
authors.lastname: Pratten
authors.forename: R J
authors.initials: RJ
authors.lastname: Newport
authors.forename: M E
authors.initials: ME
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Wilson
authors.forename: J C
authors.initials: JC
authors.lastname: Knowles
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D018441:Biofilms; D002412:Cations / Q000737:chemistry; D005708:Gallium / Q000737:chemistry*; D005898:Glass / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D010710:Phosphates / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013696:Temperature
chemical_list: D000890:Anti-Infective Agents; D002412:Cations; D010710:Phosphates; D005708:Gallium