title: On-demand antimicrobial release from a temperature-sensitive polymer - comparison with ad libitum release from central venous catheters.
abstract: Antimicrobial releasing biomaterial coatings have found application for instance in the fixation of orthopedic joint prostheses and central venous catheters. Most frequently, the release kinetics is such that antimicrobially-effective concentrations are only reached within the first days to weeks after implantation, leaving no local antimicrobial release available when a biomaterial-associated infection occurs later. Here we compare the ad libitum release of chlorhexidine and silver-sulfadiazine from a central venous catheter with their release from a new, on-demand release coating consisting of a temperature-sensitive copolymer of styrene and n-butyl (meth)acrylate. The copolymer can be loaded with an antimicrobial, which is released when the temperature is raised above its glass transition temperature. Ad libitum release of chlorhexidine and silver-sulfadiazine from a commercially-purchased catheter and associated antimicrobial efficacy against Staphylococcus aureus was limited to 16days. Consecutive temperature-triggers of our on-demand coating yielded little or no antimicrobial efficacy of silver-acetate release, but antimicrobially-effective chlorhexidine concentrations were observed over a time period of 60-80days. This attests to the clear advantage of on-demand coatings above ad libitum releasing coatings, that may have released their antimicrobial content before it is actually needed. Importantly, glass transition temperature of chlorhexidine loaded copolymers was lower (48°C) than of silver loaded ones (61°C), facilitating their clinical use.
authors.affiliation: University of Groningen and University Medical Center Groningen Department of Biomedical Engineering, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. Electronic address: j.sjollema@umcg.nl.
authors.forename: Jelmer
authors.initials: J
authors.lastname: Sjollema
authors.affiliation: University of Groningen and University Medical Center Groningen Department of Biomedical Engineering, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Rene J B
authors.initials: RJ
authors.lastname: Dijkstra
authors.affiliation: Dolphys Medical B.V., De Lismortel 31, 5612 AR Eindhoven, The Netherlands.
authors.forename: Caroline
authors.initials: C
authors.lastname: Abeln
authors.affiliation: University of Groningen and University Medical Center Groningen Department of Biomedical Engineering, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Henny C
authors.initials: HC
authors.lastname: van der Mei
authors.affiliation: Dolphys Medical B.V., De Lismortel 31, 5612 AR Eindhoven, The Netherlands.
authors.forename: Dirk
authors.initials: D
authors.lastname: van Asseldonk
authors.affiliation: University of Groningen and University Medical Center Groningen Department of Biomedical Engineering, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Busscher
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage*; D062905:Central Venous Catheters; D002710:Chlorhexidine / Q000008:administration & dosage*; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006801:Humans; D008689:Methacrylates / Q000737:chemistry; D012837:Silver Sulfadiazine / Q000008:administration & dosage*; D013203:Staphylococcal Infections / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000187:drug effects; D020058:Styrene / Q000737:chemistry; D013696:Temperature
chemical_list: D000890:Anti-Infective Agents; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D008689:Methacrylates; D020058:Styrene; D002710:Chlorhexidine; C016284:butyl methacrylate; D012837:Silver Sulfadiazine
keywords: Biofilms; Central venous catheters; Chlorhexidine; Infection; Silver