Medium-Chain Fatty Acids Released from Polymeric Electrospun Patches Inhibit Candida albicans Growth and Reduce the Biofilm Viability

Abstract

Oral candidiasis is a very common oral condition among susceptible individuals, with the main causative organism being the fungus Candida albicans . Current drug delivery systems to the oral mucosa are often ineffective because of short drug/tissue contact times as well as increased prevalence of drug-resistant Candida strains. We evaluated the potency of saturated fatty acids as antifungal agents and investigated their delivery by novel electrospun mucoadhesive oral patches using agar disk diffusion and biofilm assays. Octanoic (C8) and nonanoic (C9) acids were the most effective at inhibiting C. albicans growth on disk diffusion assays, both in solution or when released from polycaprolactone (PCL) or polyvinylpyrrolidone/RS100 (PVP/RS100) electrospun patches. In contrast, dodecanoic acid (C12) displayed the most potent antifungal activity against pre-existing C. albicans biofilms in solution or when released by PCL or PVP/RS100 patches. Both free and patch-released saturated fatty acids displayed a significant toxicity to wild-type and azole-resistant strains of C. albicans . These data not only provide evidence that certain saturated fatty acids have the potential to be used as antifungal agents but also demonstrate that this therapy could be delivered directly to Candida -infected sites using electrospun mucoadhesive patches, demonstrating a potential new therapeutic approach to treat oral thrush.

The Role of Fatty Acid Metabolites in Vaginal Health and Disease: Application to Candidiasis

“…In contrast to the growth experiment, the three longest MCFA (capric, undecanoic and lauric acid) killed the most cells in the biofilm while heptanoic, caprylic and non-anoic acid were much less effective in reducing biofilm viability. The inhibition of MCFA on C. albicans growth and biofilm formation is confirmed by various other studies, however no consensus is reached on which MCFA are most potent (Bergsson et al, 2001;Murzyn et al, 2010;Takahashi et al, 2012;Clitherow et al, 2020;Lee et al, 2020).…”

“…MCFA are fatty acids with a chain length of 6-12 carbon atoms [caproic (C6), heptanoic (C7), caprylic (C8), non-anoic (C9), capric (C10), undecanoic (C11), and lauric (C12) acid]. In multiple studies, their antifungal effect on Candida species were demonstrated (Bergsson et al, 2001;Murzyn et al, 2010;Takahashi et al, 2012;Clitherow et al, 2020;Lee et al, 2020;Suchodolski et al, 2021). In Clitherow, Binaljadm (Clitherow et al, 2020), effects of all MCFA were tested on wild-type strains (SC5314, BWP17) and an azole-resistant strain (CAR17) of C. albicans and on other Candida species.…”

“…Non-anoic acid also significantly inhibited the growth of C. auris, C. tropicalis, and C. glabrata. The effect of the MCFA were also tested on the biofilm viability of strain SC5314 (Clitherow et al, 2020). In contrast to the growth experiment, the three longest MCFA (capric, undecanoic and lauric acid) killed the most cells in the biofilm while heptanoic, caprylic and non-anoic acid were much less effective in reducing biofilm viability.…”

Electrospinning: A promising technique for drug delivery systems

“…Its systems were designed for drug delivery to the oral mucosa, the protein was released at a clinically desirable rate, reaching 90 ± 13% cumulative release after 2 h. Also, its antibacterial properties were tested against a Gram-positive Streptococcus ratti, causing bacterial cell lysis [87]. In the same context, fatty acids in poly(vinylpyrrolidone)/Eudragit RS100 electrospun mucoadhesives patches were effective as antifungal agents against the fungus candida albicans, the results showed that fatty acids could be delivered directly to Candidainfected sites [88].…”

Assessment of Conjugate Complexes of Chitosan and Urtica dioica or Equisetum arvense Extracts for the Control of Grapevine Trunk Pathogens

“…They concluded that saturated fatty acids, i.e., palmitic acid (found in E. arvense extract at high concentrations, see above), showed stronger antifungal activity than unsaturated fatty acids. The main molecular mechanism by which fatty acids are thought to act is through their direct insertion into the fungal plasma membrane, resulting in increased fluidity, deregulation of membrane proteins and altered hydrostatic turgor pressure within the cell, leading to cytoplasmic disorder and ultimately to cell death [47]. According to Pohl, et al [48], palmitic acid should result in an enhanced antifungal efficiency, which has been demonstrated against Aspergillus niger, A. terreus and Emericella nidulans by Altieri, et al [49].…”