Biofilms associated with implanted medical devices are a major source of hospital-acquired infections. C. albicans currently causes the highest number of systemic fungal infections, resulting in &gt;30% mortality rates. We have developed a materials-based approach to prevent C. albicans biofilm formation on catheter tube segments by incorporating potent antifungal β-peptides in polymer-based polyelectrolyte multilayer (PEM) coatings. β-peptides are stable synthetic mimics of antimicrobial α-peptides and are considered to be less likely to lead to acquired resistance by pathogens compared to traditional antifungal drugs. We used a fill-and-purge approach to fabricate multilayers of poly-L-glutamic acid (PGA) and poly-L-lysine (PLL) on the inner (luminal) surfaces of polyethylene catheters and loaded them post-fabrication with a coumarin-labeled antifungal β-peptide. This approach leads to a gradual release of a total of 3µg/cm2 of active β-peptide over a period of ~120 days. PEM-coated catheters loaded with β-peptide exhibited antifungal activity against planktonic C. albicans cells incubated intraluminally and also reduced the amount of biofilm formed on the inner surfaces of the catheters by ~80 % compared to untreated and PEM-coated catheter (no peptide) controls. We have also developed dual-action antifungal coatings by loading antifungal β-peptide into inherently antifungal PEMs fabricated from chitosan (CH) and hyaluronic acid (HA). We compared HA/CH and PGA/PLL films with respect to their film thicknesses, peptide loading, peptide release, and short, long-term, and multiple-trial challenges with C. albicans to assess their antifungal activities and ability to prevent biofilm formation in vitro and in vivo using a rat central venous catheter model. Overall, our results establish that both PEMs loaded with antifungal β-peptides and the inherently antifungal HA/CH PEMs alone are effective in preventing fungal biofilm formation in vitro and in vivo and demonstrate the potential of this approach to prevent medical device-associated fungal infections.

Polyelectrolyte multilayers loaded with antifungal β-peptide reduce the formation of C. albicans biofilms in film-coated catheter segments in vitro and in vivo

251st National Meeting (2016)

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