title: Polymer multilayers loaded with antifungal β-peptides kill planktonic Candida albicans and reduce formation of fungal biofilms on the surfaces of flexible catheter tubes.
abstract: Candida albicans is the most common fungal pathogen responsible for hospital-acquired infections. Most C. albicans infections are associated with the implantation of medical devices that act as points of entry for the pathogen and as substrates for the growth of fungal biofilms that are notoriously difficult to eliminate by systemic administration of conventional antifungal agents. In this study, we report a fill-and-purge approach to the layer-by-layer fabrication of biocompatible, nanoscale 'polyelectrolyte multilayers' (PEMs) on the luminal surfaces of flexible catheters, and an investigation of this platform for the localized, intraluminal release of a cationic β-peptide-based antifungal agent. We demonstrate that polyethylene catheter tubes with luminal surfaces coated with multilayers ~700nm thick fabricated from poly-l-glutamic acid (PGA) and poly-l-lysine (PLL) can be loaded, post-fabrication, by infusion with β-peptide, and that this approach promotes extended intraluminal release of this agent (over ~4months) when incubated in physiological media. The β-peptide remained potent against intraluminal inoculation of the catheters with C. albicans and substantially reduced the formation of C. albicans biofilms on the inner surfaces of film-coated catheters. Finally, we report that these β-peptide-loaded coatings exhibit antifungal activity under conditions that simulate intermittent catheter use and microbial challenge for at least three weeks. We conclude that β-peptide-loaded PEMs offer a novel and promising approach to kill C. albicans and prevent fungal biofilm formation on surfaces, with the potential to substantially reduce the incidence of device-associated infections in indwelling catheters. β-Peptides comprise a promising new class of antifungal agents that could help address problems associated with the use of conventional antifungal agents. The versatility of the layer-by-layer approach used here thus suggests additional opportunities to exploit these new agents in other biomedical and personal care applications in which fungal infections are endemic.
authors.affiliation: Department of Chemical and Biological Engineering, 1415 Engineering Drive, University of Wisconsin-Madison, Madison 53706, USA.
authors.forename: Namrata
authors.initials: N
authors.lastname: Raman
authors.affiliation: Department of Chemical and Biological Engineering, 1415 Engineering Drive, University of Wisconsin-Madison, Madison 53706, USA.
authors.forename: Myung-Ryul
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Department of Chemical and Biological Engineering, 1415 Engineering Drive, University of Wisconsin-Madison, Madison 53706, USA. Electronic address: palecek@engr.wisc.edu.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Palecek
authors.affiliation: Department of Chemical and Biological Engineering, 1415 Engineering Drive, University of Wisconsin-Madison, Madison 53706, USA; Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison 53706, USA. Electronic address: dlynn@engr.wisc.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Lynn
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D055499:Catheter-Related Infections / Q000382:microbiology / Q000517:prevention & control*; D057785:Catheters / Q000382:microbiology*; D002626:Chemistry, Pharmaceutical; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D004866:Equipment Contamination; D004867:Equipment Design; D007700:Kinetics; D011099:Polyglutamic Acid / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D011107:Polylysine; D011099:Polyglutamic Acid
keywords: Antifungal; Biofilms; Catheters; Controlled release; Polymer multilayers; Surfaces