Abstract

Due to the growing issues with fungal infections, especially with Candida, there is still a need to develop novel anti-Candida materials. One of the known antifungal agents is undecylenic acid (UA), which still cannot be efficiently used due to its oily nature, and thus limited solubility. By taking advantage of the properties of UA, we developed an emulsion with hexagonal phase, i.e., hexosomes, whose structure and morphology was studied by small-angle X-ray scattering and cryo-electron microscopy, respectively. The presence of UA in the hexosome was confirmed by spectroscopy. Moreover, we studied the anti-Candida effect of hexosomes and their cytotoxicity toward human cells. The minimal inhibitory concentration for the 50% and 90% Candida-growth reduction was found at 0.01 and 0.16 wt % hexosomes, respectively (i.e., 2 and 32 pghex/C.a.cell, respectively). The percentage of metabolically active Candida was reduced by 72–96% at hexosome concentrations of 1.0–8.2 pghex/C.a.cell as compared to untreated Candida. Furthermore, at the same concentration range the embedded filamentation test after 24 and 48 h showed the inhibition of both the filamentation and growth of Candida, while the preliminary toxicity test showed that hexosomes were nontoxic for human cells. All these render the here-developed hexosomes with UA efficient and promising anti-Candida agents.

Highlights

  • Fungal infections are recognized as one of the major health issues affecting millions of people worldwide [1,2] and Candida is among the four fungal species that pose the largest issue [1]

  • The nanocarrier formulation was obtained by mixing melted monoglycerides (i.e., Dimodan U/J, DU) with undecylenic acid (UA) and dispersing them with an ultrasonic tip in an aqueous solution containing

  • The hydrophobic moieties (i.e., PPO) of the polymer are adsorbed at the surface of the particles, whereas the hydrophilic ones (i.e., poly(ethylene oxide) blocks (PEO)) build a corona that sterically stabilizes the dispersion [32]

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Summary

Introduction

Fungal infections are recognized as one of the major health issues affecting millions of people worldwide [1,2] and Candida is among the four fungal species that pose the largest issue [1]. One recent study revealed the anti-Candida mechanisms of action of UA, which reduces the hypha-to-yeast ratio and inhibits: hyphal formation, adhesion, mitochondrial activity, cell proliferation, transcriptional regulation of the cell membrane virulent factors, and biofilm formation [30]. Considering this exceptional potential of UA against. Their physicochemical properties, such as hydrodynamic diameter, ζ-potential, chemical nature, and morphology structure, were studied by dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), cryo-electron microscopy, and small-angle X-ray scattering (SAXS), respectively. We investigated the effect of hexosomes on the morphology and growth of C.a. cells in embedded conditions after 24 and 48 h of incubation

Physicochemical Properties of Hexosomes
Anti-Candida
The effect hexosomeson onthe theCandida
Formulation of Hexosomes
Physicochemical Characterisation of Hexosomes
Microorganism and Culture Conditions
Anti-Candida Characterization of Hexosomes
XTT Assay
Embedded Filamentation Assay
Cytotoxicity Study of Hexosomes

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