The Mould War: Developing an Armamentarium against Fungal Pathogens Utilising Thymoquinone, Ocimene, and Miramistin within Bacterial Cellulose Matrices

Abstract

An increase in antifungal resistance has seen a surge in fungal wound infections in patients who are immunocompromised resulting from chemotherapy, disease, and burns. Human pathogenic fungi are increasingly becoming resistant to a sparse repertoire of existing antifungal drugs, which has given rise to the need to develop novel treatments for potentially lethal infections. Bacterial cellulose (BC) produced by Gluconacetobacter xylinus has been shown to possess many properties that make it innately useful as a next-generation biopolymer to be utilised as a wound dressing. The current study demonstrates the creation of a pharmacologically active wound dressing by loading antifungal agents into a biopolymer hydrogel to produce a novel wound dressing. Amphotericin B is known to be highly hepatotoxic, which reduces its appeal as an antifungal drug, especially in patients who are immunocompromised. This, coupled with an increase in antifungal resistance, has seen a surge in fungal wound infections in patients who are immunodeficient due to chemotherapy, disease, or injury. Antifungal activity was conducted via Clinical & Laboratory Standards Institute (CLSI) M27, M38, M44, and M51 against Candida auris, Candida albicans, Aspergillus fumigatus, and Aspergillus niger. This study showed that thymoquinone has a comparable antifungal activity to amphotericin B with mean zones of inhibition of 21.425 ± 0.925 mm and 22.53 ± 0.969 mm, respectively. However, the mean survival rate of HEp-2 cells when treated with 50 mg/L amphotericin B was 29.25 ± 0.854% compared to 71.25 ± 1.797% when treated with 50 mg/L thymoquinone. Following cytotoxicity assays against HEp-2 cells, thymoquinone showed a 71.25 ± 3.594% cell survival, whereas amphotericin B had a mean cell survival rate of 29.25 ± 1.708%. The purpose of this study was to compare the efficacy of thymoquinone, ocimene, and miramistin against amphotericin B in the application of novel antifungal dressings.

Thymoquinone: Hydroxypropyl-β-cyclodextrin Loaded Bacterial Cellulose for the Management of Wounds

“…Purified, unloaded (neat) BC was transparent confirming the removal of remnants of biomass and culture media. This is in accordance with our findings previously reported [2,20,28]. Due to the pigmentation of THQ:HPβCD, the loaded BC turned translucent, but was bright yellow in colour, suggesting successful loading of the inclusion complex.…”

“…BC production was conducted according to the protocol described in our previous paper [2,28]. A starter culture of G. xylinus was inoculated into HS media and incubated at 37 • C for 14 days in this study.…”

“…Wound healing is a highly complex physiological process. Many steps can overlap, and the order in which they occur is equally intricate [1,2].…”

“…In our previous studies the antimicrobial activity, as well as toxicity, both thymoquinone and hydroxypropyl-β-cyclodextrins (HPβCD), were shown to be well within accepted limits for use as a topical antimicrobial [1,2]. However, THQ 's highly hydrophobic nature limits a variety of biomedical applications [24][25][26].…”

Structural Significance of Hydrophobic and Hydrogen Bonding Interaction for Nanoscale Hybridization of Antiseptic Miramistin Molecules with Molybdenum Disulfide Monolayers

“…Miramistin is a broad-spectrum antiseptic of the above-mentioned type, the active moiety of which is the benzyldimethyl{3-[(1-oxotetradecyl)amino]propyl}ammonium [ 20 ], medicated as a solution of its chloride salt [ 20 , 21 , 22 ]. It was proven to be active against the various microbial and fungi infections [ 22 , 23 , 24 ] and is often considered as one of the benchmark drugs for corresponding chemotherapies [ 25 , 26 ]. The distinctive feature of MR molecular skeleton is the presence of amidopropyl linker, which is capable of playing the role of a hinge between the ammonium head and aliphatic tail ( Figure 1 ).…”