Isoniazid Conjugated Magnetic Nanoparticles Loaded with Amphotericin B as a Potent Antiamoebic Agent against Acanthamoeba castellanii.

Kawish Iqbal,Ayaz Anwar,Naveed Ahmed Khan,Areeba Anwar,Sumayah Abdelnasir Osman Abdalla,Kanwal Muhammad Iqbal,Ruqaiyyah Siddiqui,Muhammad Raza Shah

doi:10.3390/antibiotics9050276

Abstract

The pathogenic free-living amoeba, Acanthamoeba castellanii, is responsible for a rare but deadly central nervous system infection, granulomatous amoebic encephalitis and a blinding eye disease called Acanthamoeba keratitis. Currently, a combination of biguanides, amidine, azoles and antibiotics are used to manage these infections; however, the host cell cytotoxicity of these drugs remains a challenge. Furthermore, Acanthamoeba species are capable of transforming to the cyst form to resist chemotherapy. Herein, we have developed a nano drug delivery system based on iron oxide nanoparticles conjugated with isoniazid, which were further loaded with amphotericin B (ISO-NPs-AMP) to cause potent antiamoebic effects against Acanthamoeba castellanii. The IC50 of isoniazid conjugated with magnetic nanoparticles and loaded with amphotericin B was found to be 45 μg/mL against Acanthamoeba castellanii trophozoites and 50 μg/mL against cysts. The results obtained in this study have promising implications in drug discovery as these nanomaterials exhibited high trophicidal and cysticidal effects, as well as limited cytotoxicity against rat and human cells.

Highlights

Free-living amoebae Naegleria fowleri, Balamuthia mandrillaris, and Acanthamoeba castellanii cause the central nervous system infections, primary amoebic meningoencephalitis (PAM) and granulomatous amoebic encephalitis (GAE) [1]
Isoniazid-conjugated iron oxide nanoparticles loaded with amphotericin B were
Isoniazid-conjugated iron oxide nanoparticles loaded with amphotericin B were synthesized by chemical and physical interaction

Summary

Introduction

Free-living amoebae Naegleria fowleri, Balamuthia mandrillaris, and Acanthamoeba castellanii cause the central nervous system infections, primary amoebic meningoencephalitis (PAM) and granulomatous amoebic encephalitis (GAE) [1] These diseases are rare but almost always prove to be fatal with a staggering mortality rate of over 95% [2]. Nanoparticles (NPs) have attracted recent scientific attention as antimicrobial agents against a variety of microorganisms including fungi, viruses, bacteria and parasites [4,5]. Their smaller size and large surface to volume ratio makes them ideal candidates for drug delivery applications [6]

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