Assessment of nonreleasing antifungal surface coatings bearing covalently attached pharmaceuticals

Abstract

There are many reports of antimicrobial coatings bearing immobilized active agents on surfaces; however, strong analytical evidence is required to verify that the agents are indeed covalently attached to the surface. In the absence of such evidence, antimicrobial activity could result from a release of active agents. We report a detailed assessment of antifungal surface coatings prepared using covalent attachment chemistries, with the aim of establishing a set of instrumental and biological evidence required to convincingly demonstrate antimicrobial activity due to nonreleasing, surface active compounds and to exclude the alternate possibility of activity due to release. The strongest biological evidence initially supporting permanent antifungal activity was the demonstration of the ability to reuse samples in multiple, sequential pathogen challenges. However, additional supporting evidence from washing studies and instrumental analysis is also required to probe the possibility of gradual desorption of strongly physisorbed compounds versus covalently attached compounds. Potent antifungal surface coatings were prepared from approved pharmaceutical compounds from the echinocandin drug class (caspofungin, anidulafungin, and micafungin) and assessed by microbiological tests and instrumental methods. Carbonyl diimidazole linking chemistry enabled covalent attachment of caspofungin, anidulafungin, and micafungin to plasma polymer surfaces, with antifungal surface activity likely caused by molecular orientations that present the lipophilic tail toward interfacing fungal cells. This study demonstrates the instrumental and biological evidence required to convincingly ascertain activity due to nonreleasing, surface active compounds and summarize these as three criteria for assessing other reports on surface-immobilized antimicrobial compounds.

Comparison of continuous wave and pulsed mode plasma polymerization of glycidol for storage‐stable coatings for biomolecule immobilization

“…In previous work, it was shown that for samples with surface‐grafted caspofungin where XPS %N was less than 2%, it was still possible to achieve a greater than log 6 reduction of the surface attachment and growth of C. albicans . [ 75 ]…”

“…The finding that caspofungin retains its antifungal potency when grafted to a surface accords with previous work in which the antifungal mechanism was postulated to be caused by contact of the fungal cell wall with surface‐bound caspofungin molecules, facilitating their interaction with a specific enzyme in the fungal cell wall. [ 75,87 ]…”

“…Yet, the amount of caspofungin that could be bound to the surface after 2 years (1.7% N), would still be sufficient to exert a potent antifungal effect. [ 75 ] More generally, the long‐lasting binding capacity might be considered useful for medical device manufacturers interested in functionalizing medical devices with capture‐ready coatings that could be prepared ahead of time and stored. If sensitive biomolecules are needed for their function (such as proteins or peptides) these could be bound immediately before device implantation so as to preserve maximum activity.…”

Plasma polymerization for biomedical applications: A review

“…Results showed that the anidulafungin‐attached surface could be challenged at least five times while eliminating colonizing cells and preventing biofilm formation. [ 105 ] This study demonstrated that grafted antimicrobial coatings have the potential to achieve longer‐lasting deterrence than release coatings can.…”

“…XPS analysis of these surfaces shows oxygenated groups such as −OH and −COOH to which antimicrobial compounds bearing −OH, −NH 2 substituents can be coupled using carbonyldiimidazole (CDI). [104,105] After thorough washing (again using hot SDS solution), Naderi et al showed that surface-attached caspofungin, anidulafungin, and micafungin all showed potency in eliminating 10 6 CFU/cm 2 of C. albicans cells and prevention of biofilm formation. The hypothesis that covalently attached drugs could form a "permanently" active antimicrobial interface was tested by reusing the surfaces in repeat antimicrobial assays with fresh microbial challenges.…”