Bactericidal Activity of Usnic Acid-Chitosan Nanoparticles against Persister Cells of Biofilm-Forming Pathogenic Bacteria

Abstract

The present study aimed to prepare usnic acid (UA)-loaded chitosan (CS) nanoparticles (UA-CS NPs) and evaluate its antibacterial activity against biofilm-forming pathogenic bacteria. UA-CS NPs were prepared through simple ionic gelification of UA with CS, and further characterized using Fourier transform infrared spectroscopy, X-ray diffraction, and field-emission transmission electron microscopy. The UA-CS NPs presented a loading capacity (LC) of 5.2%, encapsulation efficiency (EE) of 24%, and a spherical shape and rough surface. The maximum release of UA was higher in pH 1.2 buffer solution as compared to that in pH 6.8 and 7.4 buffer solution. The average size and zeta potential of the UA-CS NPs was 311.5 ± 49.9 nm in diameter and +27.3 ± 0.8 mV, respectively. The newly prepared UA-CS NPs exhibited antibacterial activity against persister cells obtained from the stationary phase in batch culture, mature biofilms, and antibiotic-induced gram-positive and gram-negative pathogenic bacteria. Exposure of sub-inhibitory concentrations of UA-CS NPs to the bacterial cells resulted in a change in morphology. The present study suggests an alternative method for the application of UA into nanoparticles. Furthermore, the anti-persister activity of UA-CS NPs may be another possible strategy for the treatment of infections caused by biofilm-forming pathogenic bacteria.

Sustained release of usnic acid from graphene coatings ensures long term antibiofilm protection

“…However, poor solubility of UA limits its medical application 37 . In order to improve delivery and expand the scope of antibacterial applications of UA, this bioactive molecule has been incorporated into liposomes, nano emulsions and polymeric and metallic nanoparticles 37 , 38 . These strategies were effective in delivery of UA for several applications, e.g.…”

“…These strategies were effective in delivery of UA for several applications, e.g. wound treatment and targeted delivery into macrophages infected with Mycobacterium tuberculosis 37 , 38 .…”

Fabrication of bio-engineered chitosan nanoformulations to inhibition of bacterial infection and to improve therapeutic potential of intestinal microflora, intestinal morphology, and immune response in infection induced rat model

“…Though size of the particles could precisely administrate particle distributions into the body, zeta potential importantly regulates the stability of the particles and influences interactions of the nanoformulation and cell membrane. As reported previously, zeta potential value of the stable nanoformulations should be more than ±30 mV and can be highly suitable for the drug delivery system (Khan et al., 2020 ). The increasing particles size of CS NPs after cur/amp loading demonstrates the successful encapsulation of Cur/AMP molecules on the surface.…”

Nanoparticles Promote Bacterial Antibiotic Tolerance via Inducing Hyperosmotic Stress Response

“…Previously, some works have paid attention to persisters and conducted research on nanomaterials against this small subpopulation of bacteria cells. [ 26,27 ] However, when NPs with antibacterial properties (Cu, Ag, and ZnO NPs) were applied, the number of persisters did not decrease as we expected but surprisingly increased. The same results were also found for widely used NPs that did not display antimicrobial properties, including TiO 2 , SiO 2 , and Fe 3 O 4 NPs.…”