Journal
JOURNAL OF CONTROLLED RELEASE
Volume 191, Issue -, Pages 54-62Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2014.05.026
Keywords
Antifungal; Biofilms; Catheters; Controlled release; Polymer multilayers; Surfaces
Funding
- NIAID NIH HHS [1R01 AI092225, R01 AI092225] Funding Source: Medline
Ask authors/readers for more resources
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 beta-peptide-based antifungal agent. We demonstrate that polyethylene catheter tubes with luminal surfaces coated with multilayers similar to 700 nm thick fabricated from poly-L-glutamic acid (PGA) and poly-L-lysine (PLL) can be loaded, post-fabrication, by infusion with beta-peptide, and that this approach promotes extended intraluminal release of this agent (over similar to 4 months) when incubated in physiological media. The beta-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 beta-peptide-loaded coatings exhibit antifungal activity under conditions that simulate intermittent catheter use and microbial challenge for at least three weeks. We conclude that beta-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. beta-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. (C) 2014 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available