Combatting fungal biofilm formation by diffusive release of fluconazole from heptylamine plasma polymer coating

Abstract

A drug-eluting coating applied onto biomedical devices and implants is an appropriate way to ensure that an inhibitory concentration of antimicrobial drugs is present at the device surface, thus preventing surface colonization and subsequent biofilm formation. In this study, a thin polymer coating was applied to materials, and it acted as a drug-delivery reservoir capable of surface delivery of the antifungal drug fluconazole to amounts up to 21 μg/cm2. The release kinetics into aqueous solution were quantified by UV spectroscopy and conformed to the Ritger–Peppas and Korsmeyer–Peppas model. Complementary microbiological assays were used to determine effectiveness against Candida albicans attachment and biofilm formation, and against the control heptylamine plasma polymer coating without drug loading, on which substantial fungal growth occurred. Fluconazole release led to marked antifungal activity in all assays, with log 1.6 reduction in CFUs/cm2. Cell viability assays and microscopy revealed that fungal cells attached to the fluconazole-loaded coating remained rounded and did not form hyphae and biofilm. Thus, in vitro screening results for fluconazole-releasing surface coatings showed efficacy in the prevention of the formation of Candida albicans biofilm.

Amine-Rich Coatings to Potentially Promote Cell Adhesion, Proliferation and Differentiation, and Reduce Microbial Colonization: Strategies for Generation and Characterization

“…Recently, heptylamine coating has been used as a matrix for the release of fluconazole, an antifungal drug. Results showed a significant reduction in C. albicans colonies after 48 h due to a controlled release of the drug [27].…”

“…These amine-rich coatings have been studied to control cell behavior demonstrating a positive effect on cell adhesion, proliferation, and differentiation for different cell types such as osteoblast-like cells [15,20,21] and fibroblasts [16]. Moreover, these coatings could be used to incorporate molecules such as enzymes, or drugs [9,27], as well as particles such as silver nanoparticles [10] to endow the material with new desirable biological properties. The application of such coatings on cell behavior, molecules' immobilization, and antimicrobial applications are elaborated in the following sections and summarized in Table 1.…”

“…Substrate pores were loaded with vancomycin drug and were reduced by plasma polymer deposition to allow a controlled drug release [33] Low-density polyethylene Bonding of antibacterial agents by immersion of the coatings in antibacterial solutions [9] 1-vinylimidazole Thin-film composite membranes Enhanced AgNPs binding onto the plasma-treated substrates which cause a decrease in E.coli growth [10] Heptylamine Si/Glass/Thermanox plastic/Cell culture plate Release of antifungal drug [27] 2.2.1. Effect on Cell Behavior By using a gas containing amine groups, the material surface may be covered by an amine-rich coating.…”

“…Collagen coated on plasma-treated samples seems to be more resistant to PBS rinsing due to interactions between collagen and plasma-treated surfaces. Finally, different molecules, such as silver nanoparticles [10] or drugs [9,27,33], have been incorporated in these coatings to make them antibacterial, which will be discussed in the following part.…”

Plasma polymerization for biomedical applications: A review

“…Naderi et al prepared a water-stable heptylamine plasma polymer coating approximately 100 nm thick which acted as a reservoir for loading and releasing the antifungal drug fluconazole. [83] Activity against C. albicans was assayed using three different microbial assays: the agar diffusion method, a contact-kill method, and static biofilm assay. Antifungal activity was measured to be of the order of 2 logs.…”