Abstract
Herein, we report green synthesized nanoparticles based on stabilization by plant gums, loaded with citrus fruits flavonoids Hesperidin (HDN) and Naringin (NRG) as novel antimicrobial agents against brain-eating amoebae and multi-drug resistant bacteria. Nanoparticles were thoroughly characterized by using zetasizer, zeta potential, atomic force microscopy, ultravoilet-visible and Fourier transform-infrared spectroscopic techniques. The size of these spherical nanoparticles was found to be in the range of 100–225 nm. The antiamoebic effects of these green synthesized Silver and Gold nanoparticles loaded with HDN and NRG were tested against Acanthamoeba castellanii and Naegleria fowleri, while antibacterial effects were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and neuropathogenic Escherichia coli K1. Amoebicidal assays revealed that HDN loaded Silver nanoparticles stabilized by gum acacia (GA-AgNPs-HDN) quantitatively abolished amoeba viability by 100%, while NRG loaded Gold nanoparticles stabilized by gum tragacanth (GT-AuNPs-NRG) significantly reduced the viability of A. castellanii and N. fowleri at 50 µg per mL. Furthermore, these nanoparticles inhibited the encystation and excystation by more than 85%, as well as GA-AgNPs-HDN only completely obliterated amoeba-mediated host cells cytopathogenicity. Whereas, GA-AgNPs-HDN exhibited significant bactericidal effects against MRSA and E. coli K1 and reduced bacterial-mediated host cells cytotoxicity. Notably, when tested against human cells, these nanoparticles showed minimal (23%) cytotoxicity at even higher concentration of 100 µg per mL as compared to 50 µg per mL used for antimicrobial assays. Hence, these novel nanoparticles formulations hold potential as therapeutic agents against infections caused by brain-eating amoebae, as well as multi-drug resistant bacteria, and recommend a step forward in drug development.
Highlights
Brain-eating amoebae are pathogenic protists and causative agents for deadly central nervous system (CNS) infections including primary amoebic encephalitis (PAM) and granulomatous amoebic encephalitis (GAE)[1]
Smaller the size of the nanoparticles greater will be the surface to volume ratio, the chances of interactions between the bioactive drug molecules and the nanoparticles increases which enhances the therapeutic efficacy of the drug[32]
We synthesized silver and gold nanoparticles stabilized with plant gums and loaded them with two most common citrus fruits flavonoids HDN and NRG to utilize their antimicrobial activity against brain-eating parasites A. castellanii and N. fowleri and multi-drug resistant bacteria methicillin-resistant Staphylococcus aureus (MRSA) and neuropathogenic E. coli K1
Summary
Brain-eating amoebae are pathogenic protists and causative agents for deadly central nervous system (CNS) infections including primary amoebic encephalitis (PAM) and granulomatous amoebic encephalitis (GAE)[1]. Our research showed that Amphotericin B, Nystatin and Fluconazole conjugated AgNPs showed enhanced antiamoebic activity against brain-eating N. fowleri and A. castellanii[21,22] Natural compounds such as cinnamic acid[23], periglaucine A, betulinic acid[24], and tannic acid[25] coated nanomaterials have been shown to be effective against A. castellanii. Based on these reports, we synthesized HDN and NRG loaded silver and gold nanoparticles stabilized by plant gums GA and GT respectively by utilizing green synthesis protocols. These nanoparticles hold promise for further evaluation of mechanism and in vivo studies against infectious diseases caused by free-living amoeba and multi-drug resistant bacteria
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