Multitask Imidazolium Salt Additives for Innovative Poly(l-lactide) Biomaterials: Morphology Control, Candida spp. Biofilm Inhibition, Human Mesenchymal Stem Cell Biocompatibility, and Skin Tolerance

Abstract

Candida species have great ability to colonize and form biofilms on medical devices, causing infections in human hosts. In this study, poly(l-lactide) films with different imidazolium salt (1-n-hexadecyl-3-methylimidazolium chloride (C16MImCl) and 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C16MImMeS)) contents were prepared, using the solvent casting process. Poly(l-lactide)-imidazolium salt films were obtained with different surface morphologies (spherical and directional), and the presence of the imidazolium salt in the surface was confirmed. These films with different concentrations of the imidazolium salts C16MImCl and C16MImMeS presented antibiofilm activity against isolates of Candida tropicalis, Candida parapsilosis, and Candida albicans. The minor antibiofilm concentration assay enabled one to determine that an increasing imidazolium salt content promoted, in general, an increase in the inhibition percentage of biofilm formation. Scanning electron microscopy micrographs confirmed the effective prevention of biofilm formation on the imidazolium salt containing biomaterials. Lower concentrations of the imidazolium salts showed no cytotoxicity, and the poly(l-lactide)-imidazolium salt films presented good cell adhesion and proliferation percentages with human mesenchymal stem cells. Furthermore, no acute microscopic lesions were identified in the histopathological evaluation after contact between the films and pig ear skin. In combination with the good morphological, physicochemical, and mechanical properties, these poly(l-lactide)-based materials with imidazolium salt additives can be considered as promising biomaterials for use in the manufacturing of medical devices.

Alkylimidazolium Ionic Liquids as Antifungal Alternatives: Antibiofilm Activity Against Candida albicans and Underlying Mechanism of Action

“…Cytotoxicity data for 1-dodecyl-3-methylimidazolium iodide is not available, although it can be predicted to possess the toxicity between -decyl and -hexadecyl alkyl group containing imidazolium ionic liquids. The concentrations of 1-hexaydecyl-3-methylimidazolium chloride at 0.84 µg ml −1 and 1.69 µg ml −1 for antifungal and antibiofilm (for complete biofilm prevention) activities, respectively, are below the reported toxicity value of 10 µg ml −1 on fibroblast cells (Schrekker et al, 2016) and seems to be safe. Nevertheless, additional biocompatibility studies of antifungal ionic liquids are warranted for considering these compounds in prospective formulations.…”

“…The results of in vitro assays are useful for guiding treatment choices (Beardsley et al, 2018) and complementation with in vivo studies is necessary for considering potential clinical applications. Schrekker et al (2016) evaluated the biocompatibility of imidazolium ionic liquids in vitro using L929 fibroblast cells of mice. These tests revealed that cytotoxicity increases with an increase in alkyl chain length from -butyl to -decyl andhexadecyl group.…”

“…Antifungal ionic liquids were incorporated into poly(L-lactide) biomaterials for inhibiting adhesion of Candida spp. (Schrekker et al, 2016). Using contaminated acrylic resin strip specimens, 1-n-hexadecyl-3-methylimidazolium chloride was demonstrated as a strong antifungal for mouthwash formulation (Bergamo et al, 2016).…”

Advances in Biomaterials for the Prevention and Disruption of Candida Biofilms

“…AQACs have been shown to disrupt mature Candida biofilms by interacting electrostatically with the negatively charged biofilm surface (Jung et al, 2020). Coatings with other polymers including imidazolium salt (IS) conjugated poly(L-lactide) (PLA) have also been used to effectively prevent Candida attachment on coated surfaces (Schrekker et al, 2016).…”

Imidazolium salts as alternative compounds to control diseases caused by plant pathogenic bacteria

“…They are derivatives of the imidazolium cation and an inorganic or organic anion (Riduan and Zhang ). In medicine and human health, imidazolium salts have been tested for a wide range of applications, such as antifungal (Schrekker et al ), fungal antibiofilm (Raucci et al ), antibacterial (Czekański et al ; Doria et al ), antiparasitic (Martins et al ) and larvicidal (Goellner et al ) agents. With regard to the potential use of imidazolium salts in agriculture, so far, only the results of a single study have been reported.…”