Abstract
Fungal infections caused by Candida spp. represent an emerging problem during treatment of immunocompromised patients and those hospitalized with serious principal diseases. The ever-growing number of fungal strains exhibiting drug resistance necessitates the development of novel antimicrobial therapies including those based on membrane-permeabilizing agents and nanomaterials as drug carriers. In this study, the fungicidal activities of LL-37 peptide, ceragenin CSA-13 and its magnetic derivatives (MNP@LL-37, MNP@CSA-13) against laboratory and clinical strains of C. albicans, C. glabrata and C. tropicalis were evaluated. These experiments confirm the high anti-fungal activity of these well-characterized agents mediated by their interaction with the fungal membrane and demonstrate elevated activity following immobilization of LL-37 and CSA-13 on the surface of magnetic nanoparticles (MNPs). Furthermore, MNP-based nanosystems are resistant to inhibitory factors present in body fluids and effectively inhibit formation of fungal biofilm. Simultaneously, synthesized nanostructures maintain immunomodulatory properties, described previously for free LL-37 peptide and CSA-13 substrate and they do not interfere with the proliferation and viability of osteoblasts, confirming their high biocompatibility.
Highlights
Over the last 40 years the number of fungal infections has continued to grow
Based on Thermogravimetric analysis (TGA)-weight lost and total amount of amine groups on the magnetic nanoparticles (MNPs) surface, we calculated that the number of CSA-13 molecules was 3.53 × 1013, which corresponds to a number of molecules 20 times lower per 1 μg of compound[22, 23]
It is established that the mechanism of antimicrobial activity of magnetic nanoparticles involves generation of reactive oxygen species (ROS) followed by disruption in bacterial electron transport of oxidation of NADH
Summary
Over the last 40 years the number of fungal infections has continued to grow. More than 70% of these cases are caused by Candida spp, especially in the large population of patients with immune disorders and/or those hospitalized with serious underlying diseases[1, 2]. The treatment of yeast infections often requires the use of combined therapy, including additional therapeutic substances from the group of antibiotics and steroids. Certain classes of nanomaterials, initially proposed as drug carriers in the delivery of chemotherapeutic agents, have been investigated in both in vitro and in vivo settings[13,14,15,16] Metallic nanoparticles such as silver, gold, selenium, and ferrum are characterized by inherent antimicrobial properties[17]. We observe that immobilization of cationic lipids on the magnetic carrier enhances their antifungal activity compared to unattached compounds in the presence of different body fluids These nanosystems are characterized by lower lytic activity against osteoblasts indicating their improved biocompatibility. Nanoparticles functionalized by cationic lipids did not increase the release of the proinflammatory cytokine IL-8 and do not interfere with cell proliferation at concentration sufficient to induce antifungal effect
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