Metronidazole conjugated magnetic nanoparticles loaded with amphotericin B exhibited potent effects against pathogenic Acanthamoeba castellanii belonging to the T4 genotype

Sumayah Abdelnasir,Muhammad Kawish,Ruqaiyyah Siddiqui,Muhammad Raza Shah,Ayaz Anwar,Areeba Anwar,Naveed Ahmed Khan

doi:10.1186/s13568-020-01061-z

Abstract

Acanthamoeba castellanii can cause granulomatous amoebic encephalitis and Acanthamoeba keratitis. Currently, no single drug has been developed to effectively treat infections caused by Acanthamoeba. Recent studies have shown that drugs conjugated with nanoparticles exhibit potent in vitro antiamoebic activity against pathogenic free-living amoebae. In this study, we have developed a nano drug delivery system based on iron oxide nanoparticles conjugated with metronidazole which were further loaded with amphotericin B to produce enhanced antiamoebic effects against Acanthamoeba castellanii. The results showed that metronidazole-nanoparticles-amphotericin B (Met-MNPs-Amp) significantly inhibited the viability of these amoebae as compared to the respective controls including drugs and nanoparticles alone. Met-MNPs-Amp exhibited IC50 at 50 μg/mL against both A. castellanii trophozoites and cysts. Furthermore, these nanoparticles did not affect the viability of rat and human cells and showed safe hemolytic activity. Hence, the results obtained in this study have potential utility in drug development against infections caused by Acanthamoeba castellanii. A combination of drugs can lead to successful prognosis against these largely neglected infections. Future studies will determine the value of conjugating molecules with diagnostic and therapeutic potential to provide theranostic approaches against these serious infections.

Highlights

Nanoparticles (NPs) are proven future antimicrobials against bacteria, fungi, viruses, and parasites because of their broad activities against microbes including but not limited to the production of reactive oxygen species, DNA interaction, and metabolic functions (Hoseinzadeh et al 2017; Vimbela et al 2017; Wang et al 2017)
These findings suggest that nanoparticles are valuable in developing future treatments against these deadly infections (Anwar et al 2018). These findings are not surprising as metronidazole is a common antiprotozoal drug used against Giardia and Entamoeba and Trichomonas (Freeman et al 1997). It has been the part of regimen used to treat cases of primary amoebic meningoencephalitis (PAM) (Gupta et al 2015; Deetz et al 2003)
Amphotericin B conjugated with gold and silver nanoparticles have shown enhanced antiamoebic effects against A. castellanii and N. fowleri (Anwar et al 2019b; Rajendran et al 2017)

Summary

Introduction

Nanoparticles (NPs) are proven future antimicrobials against bacteria, fungi, viruses, and parasites because of their broad activities against microbes including but not limited to the production of reactive oxygen species, DNA interaction, and metabolic functions (Hoseinzadeh et al 2017; Vimbela et al 2017; Wang et al 2017). These characteristics of metallic nanoparticles improve the capacity of drug development against infectious diseases. Nanoparticle conjugation with broad spectrum antibiotics and natural products, has been found to be an effective strategy against brain-eating amoebae, N. fowleri (Anwar et al 2019b, c; Rajendran et al 2017)

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