Formulation and candidacidal activity of magnetic nanoparticles coated with cathelicidin LL-37 and ceragenin CSA-13

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.

Antimicrobial and Physicochemical Properties of Artificial Saliva Formulations Supplemented with Core-Shell Magnetic Nanoparticles

“…Proposed nanostructures possess well-defined physicochemical properties and proven antibacterial activity. According to published literature [35][36][37], the proposed mode of antibacterial action of magnetic nanoparticles involves their contribution in the induction of oxidative stress, via generation of reactive oxygen species (ROS), as well as Our previous studies [38][39][40][41] have shown that they interact in a synergistic or additive manner, with chemotherapeutic agents used in standard antimicrobial treatment, as well as with a representative of antimicrobial peptides that take part in the immune-defense process and with their synthetic mimetics. Here we describe how the presence of magnetic nanoparticles might lead to improving the antimicrobial properties of artificial saliva substitutes ( Figure 3).…”

“…In turn, in the aspect of viability of cells embedded in biofilm mass, addition of tested substitutes supplemented by magnetic nanoparticles indicated that means reduction of viable cell was calculated at the level 55 % in the case of fungal cells, 40% in the case of Gram-positive bacteria and 50 % for P. aeruginosa (Figure 3d). Our previous studies [38][39][40][41] have shown that they interact in a synergistic or additive manner, with chemotherapeutic agents used in standard antimicrobial treatment, as well as with a representative of antimicrobial peptides that take part in the immune-defense process and with their synthetic mimetics. Here we describe how the presence of magnetic nanoparticles might lead to improving the antimicrobial properties of artificial saliva substitutes ( Figure 3).…”

Bactericidal and immunomodulatory properties of magnetic nanoparticles functionalized by 1,4-dihydropyridines

“…This result was additionally confirmed by X-ray diffraction analysis and is in agreement with our previously published studies. 15,26 antimicrobial activity of 1,4-DhPs Antimicrobial activity was evaluated against representative strains of Gram-positive bacteria, Gram-negative bacteria and fungi. The analysis involved laboratory and clinical isolates of frequently occurring pathogenic strains including S. aureus, E. coli, P. aeruginosa, and Candida sp.…”

Ceragenins as non-peptide mimics of endogenous antimicrobial peptides

“…In a recent study, LL-37 or CSA-13 immobilized on magnetic nanoparticles were to shown to increase ROS generation in fungal cells, suggesting an additional pathway of antifungal activity with Candida spp. (Figure 3) [79]. Nevertheless, additional information is still required to fully understand how ceragenins target and kill fungal cells.…”