Bactericidal activity and biocompatibility of ceragenin-coated magnetic nanoparticles

Abstract

Background: Ceragenins, synthetic mimics of endogenous antibacterial peptides, are promising candidate antimicrobial agents. However, in some settings their strong bactericidal activity is associated with toxicity towards host cells. To modulate ceragenin CSA-13 antibacterial activity and biocompatibility, CSA-13-coated magnetic nanoparticles (MNP-CSA-13) were synthesized. Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to characterize MNP-CSA-13 physicochemical properties. Bactericidal action and ability of these new compounds to prevent Pseudomonas. aeruginosa biofilm formation were assessed using a bacteria killing assay and crystal violet staining, respectively. Release of hemoglobin from human red blood cells was measured to evaluate MNP-CSA-13 hemolytic activity. In addition, we used surface activity measurements to monitor CSA-13 release from the MNP shell. Zeta potentials of P. aeruginosa cells and MNP-CSA-13 were determined to assess the interactions between the bacteria and nanoparticles. Morphology of P. aeruginosa subjected to MNP-CSA-13 treatment was evaluated using atomic force microscopy (AFM) to determine structural changes indicative of bactericidal activity. Results: Our studies revealed that the MNP-CSA-13 nanosystem is stable and may be used as a pH control system to release CSA-13. MNP-CSA-13 exhibits strong antibacterial activity, and the ability to prevent bacteria biofilm formation in different body fluids. Additionally, a significant decrease in CSA-13 hemolytic activity was observed when the molecule was immobilized on the nanoparticle surface. Conclusion: Our results demonstrate that CSA-13 retains bactericidal activity when immobilized on a MNP while biocompatibility increases when CSA-13 is covalently attached to the nanoparticle.

Ceragenins as Mimics of Endogenous Antimicrobial Peptides

“…The amines in ceragenins reversibly form Schiff bases (imines), which allow the nanoparticles to aggregate ceragenins [103]. Hayes et al [101] prepared silver nanoparticles coated with CSA-124 and found that they were five times more bactericidal than silver alone, with MICs against S. aureus and E. coli of ca.…”

“…12 and 24 ppm respectively. Bucki et al [103] showed that ceragenin-coated, magnetic nanoparticles retained potent bactericidal activity. In addition, sequestering ceragenins on nanoparticles enhanced biocompatibility.…”

The intrinsic antimicrobial activity of citric acid-coated manganese ferrite nanoparticles is enhanced after conjugation with the antifungal peptide Cm-p5

“…16 Additionally, ceragenin CSA-13-coated MNPs (MNP-CSA-13) exhibited strong antibacterial activity and the ability to prevent bacterial biofilm formation in different body fluids, with a significant decrease in its hemolytic activity when the molecule was immobilized on the nanoparticle surface. 17 In contrast, it has been reported that iron-containing nanoparticles may influence the ability of bacteria to absorb iron for growth, increase virulence, and inhibit AMP function. 18 Here, we present the intrinsic antifungal activity of the citric acid-coated MnFe 2 O 4 -NPs and the improvement of their antifungal activity when these nanoparticles were conjugated with a 12 aa peptide named Cm-p5.…”

Use of magnetic nanoparticles as a drug delivery system to improve chlorhexidine antimicrobial activity

“…19,20 Studies show that the immobilization/encapsulation process improves the overall biological effectiveness of active agents including pharmacokinetic parameters (bioavailability, clearance) and reduces the side effects. [21][22][23] In addition, it has been noted that the antibiotic resistance of drug-resistant pathogens may be overcome by using nanoparticles as antibiotic carriers. 24 Among the many types of nanostructures, core-shell magnetic iron oxide nanoparticles are the most commonly used drug carriers in biomedical studies.…”

“…Our previous studies indicate that the immobilization of ceragenin on the MNP surface increases its antibacterial activity in the presence of body fluids. 22 In addition, recent work suggests that the application of nanosystems composed of MNPs and polyene antibiotic may be used for the treatment of infections caused by polyeneresistant fungal strain. 29 In the present study, we evaluate the activity of magnetic nanosystems functionalized with chlorhexidine against clinical isolates of pathogens from different groups including representatives of Gram-positive and Gram-negative bacteria and fungal cells.…”