title: Effect of novel antibacterial gallium-carboxymethyl cellulose on Pseudomonas aeruginosa.
abstract: Gallium has emerged as a new therapeutic agent due partly to the scarcity in development of new antibiotics. In this study, a novel antibacterial gallium exchanged carboxymethyl cellulose (Ga-CMC) has been developed and tested for the susceptibility on a common bacteria, Pseudomonas aeruginosa. The results show that an increase in average molecular weight (MW) from 90 k, 250 k to 700 k of Ga-CMC caused a decrease in antimicrobial activity against planktonic P. aeruginosa. Gallium loading of the Ga-CMC (250 k) samples was altered by varying the amount of functionality (0.7, 0.9 and 1.2 acid groups per mole of carbohydrate) which affected also its antimicrobial activity against planktonic P. aeruginosa. Further, the ability to prevent the growth of biofilms of P. aeruginosa was tested on MW = 250 k samples with 0.9 acid groups per mole of carbohydrate as this sample showed the most promising activity against planktonic P. aeruginosa. Gallium was found to reduce biofilm growth of P. aeruginosa with a maximum effect (0.85 log(10) CFU reduction compared to sodium-carboxymethyl cellulose, Na-CMC) after 24 h. Results of the solubility and ion exchange studies show that this compound is suitable for the controlled release of Ga(3+) upon their breakdown in the presence of bacteria. SEM EDX analysis confirmed that Ga(3+) ions are evenly exchanged on the cellulose surface and systematic controls were carried out to ensure that antibacterial activity is solely due to the presence of gallium as samples intrinsic acidity or nature of counterion did not affect the activity. The results presented here highlight that Ga-CMC may be useful in controlled drug delivery applications, to deliver gallium ions in order to prevent infections due to P. aeruginosa biofilms.
authors.affiliation: Department of Health Services Research and School of Dentistry, University of Liverpool, The Research Wing, Daulby Street, Liverpool, L69 3GN, UK. s.valappil@liv.ac.uk
authors.forename: Sabeel P
authors.initials: SP
authors.lastname: Valappil
authors.forename: Humphrey H P
authors.initials: HH
authors.lastname: Yiu
authors.forename: Laurent
authors.initials: L
authors.lastname: Bouffier
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Hope
authors.forename: Gary
authors.initials: G
authors.lastname: Evans
authors.forename: John B
authors.initials: JB
authors.lastname: Claridge
authors.forename: Susan M
authors.initials: SM
authors.lastname: Higham
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Rosseinsky
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry*; D052978:Disk Diffusion Antimicrobial Tests; D005708:Gallium / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D005708:Gallium; D002266:Carboxymethylcellulose Sodium