Materials with Fungi-Bioinspired Surface for Efficient
Binding and Fungi-Sensitive Release of Antifungal Agents
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Abstract
Materials with fungi-bioinspired
surface have been designed to
host ergosterol-binding polyene antibiotics and to release them via
a competitive mechanism only when fungi are present in the medium.
Silicone rubber (SR) surfaces were endowed with selective loading
and fungi-triggered release of polyene antifungal agents by means
of a two-step functionalization that involved the grafting of glycidyl
methacrylate (GMA) via a γ-ray preirradiation method (9–21.3%
wt grafting) and the subsequent immobilization of ergosterol (3.9–116.8
mg/g) to the epoxy groups of polyGMA. The functionalized materials
were characterized using FTIR and Raman spectroscopy, thermogravimetric
analysis (TGA), and fluorescence, scanning electron microscopy (SEM),
and atomic force microscopy (AFM) image analyses. Specific interactions
between natamycin or nystatin and ergosterol endowed SR with ability
to take up these polyene drugs, while immobilization of ergosterol
did not modify the loading of antifungal drugs that did not interact
in vivo with ergosterol (e.g., miconazole). In a buffer medium, polyene-loaded
ergosterol-immobilized slabs efficiently retained the drug (<10%
released at day 14), while in the presence of ergosterol-containing
liposomes that mimic fungi membranes the release rate was 10-to-15-fold
enhanced due to a competitive displacement of the drug from the ergosterol-immobilized
slab to the ergosterol-containing liposomes. Release in the presence
of cholesterol liposomes was slower due to a weaker interaction with
polyene agents. The fungi-responsive release was demonstrated for
both polyene drugs tested and for slabs prepared with a wide range
of amounts of immobilized GMA and ergosterol, demonstrating the robustness
of the approach. Nystatin-loaded functionalized slabs were challenged
with Candida albicans and showed improved
capability to inhibit biofilm formation compared to nystatin-soaked
pristine SR, confirming the performance of the bioinspired materials