title: Biological performance of a novel synthetic furanone-based antimicrobial.
abstract: Infection of medical devices causes significant morbidity and mortality and considerable research effort has been directed at solving this problem. The aim of this study was to assess the biological performance of a novel furanone compound that has potential as an anti-infective coating for medical devices. This study examined in vitro leukocyte response following exposure to the antibacterial 3-(1'-bromohexyl)-5-dibromomethylene-2(5H)-furanone and assessed the tissue response following subcutaneous implantation of the furanone compound covalently bound to polystyrene (PS). Peripheral human blood was exposed to furanones in solution for 1h and flow cytometry used to analyse viability and changes in expression of surface receptors CD11b/CD18 and CD44. Flow cytometry results from propidium iodide stained cell suspensions suggested that the leukocytes were viable after exposure to furanones in whole blood. No significant difference was found in the expression of CD11b/CD18 and CD44 between the furanone exposed samples and the negative control for neutrophils suggesting that the furanones themselves do not activate these leukocytes. The positive control lipopolysaccharide significantly up-regulated CD11b/CD18 and slightly down-regulated CD44 on both PMNs and monocytes. In vivo studies of the tissue response to furanone covalently bound to PS showed that there was no significant difference in cellularity of capsules surrounding the disk and no significant increase in myeloperoxidase expression. These results demonstrate negligible acute inflammatory response to synthetic brominated antibacterial furanones. Future studies will focus on chronic responses and examination of in vivo efficacy.
authors.affiliation: Graduate School of Biomedical Engineering, University of New South Wales, Sydney NSW 2052, Australia.
authors.forename: J K
authors.initials: JK
authors.lastname: Baveja
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: R E
authors.initials: RE
authors.lastname: Nordon
authors.forename: E B H
authors.initials: EB
authors.lastname: Hume
authors.forename: N
authors.initials: N
authors.lastname: Kumar
authors.forename: M D P
authors.initials: MD
authors.lastname: Willcox
authors.forename: L A
authors.initials: LA
authors.lastname: Poole-Warren
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D039481:CD11b Antigen / Q000096:biosynthesis; D018821:CD18 Antigens / Q000096:biosynthesis; D002460:Cell Line; D015536:Down-Regulation; D004926:Escherichia coli / Q000378:metabolism; D005434:Flow Cytometry; D005663:Furans / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000737:chemistry; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000737:chemistry; D051379:Mice; D008956:Models, Chemical; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011108:Polymers / Q000737:chemistry; D011419:Propidium / Q000737:chemistry; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C494387:3-(1'-bromohexyl)-5-dibromomethylene-2(5H)-furanone; D000890:Anti-Infective Agents; D039481:CD11b Antigen; D018821:CD18 Antigens; D005663:Furans; D018960:Hyaluronan Receptors; D008070:Lipopolysaccharides; D011108:Polymers; D011419:Propidium; D009195:Peroxidase