Pre-clinical study of iron oxide nanoparticles fortified artesunate for efficient targeting of malarial parasite

Abstract

Background Artesunate the most potent antimalarial is widely used for the treatment of multidrug-resistant malaria. The antimalarial cytotoxicity of artesunate has been mainly attributed to its selective, irreversible and iron- radical-mediated damage of parasite biomolecules. In the present research, iron oxide nanoparticle fortified artesunate was tested in P. falciparum and in an experimental malaria mouse model for enhancement in the selectivity and toxicity of artesunate towards parasite. Artesunate was fortified with nontoxic biocompatible surface modified iron oxide nanoparticle which is specially designed and synthesized for the sustained pH-dependent release of Fe 2+ within the parasitic food vacuole for enhanced ROS spurt. Methods Antimalarial efficacy of Iron oxide nanoparticle fortified artesunate was evaluated in wild type and artemisinin-resistant Plasmodium falciparum (R539T) grown in O + ve human blood and in Plasmodium berghei ANKA infected swiss albino mice. Internalization of nanoparticles, the pH-dependent release of Fe 2+ , production of reactive oxygen species and parasite biomolecule damage by iron oxide nanoparticle fortified artesunate was studied using various biochemical, biophysical, ultra-structural and fluorescence microscopy. For determining the efficacy of ATA-IONP+ART on resistant parasite ring survival assay was performed. Results The nanoparticle fortified artesunate was highly efficient in the 1/8th concentration of artesunate IC 50 and led to retarded growth of P. falciparum with significant damage to macromolecules mediated via enhanced ROS production. Similarly, preclinical In vivo studies also signified a radical reduction in parasitemia with ~8–10-fold reduced dosage of artesunate when fortified with iron oxide nanoparticles. Importantly, the ATA-IONP combination was efficacious against artemisinin-resistant parasites. Interpretation Surface coated iron-oxide nanoparticle fortified artesunate can be developed into a potent therapeutic agent towards multidrug-resistant and artemisinin-resistant malaria in humans. Fund This study is supported by the Centre for Study of Complex Malaria in India funded by the National Institute of Health, USA.

Promising nanomaterials in the fight against malaria

“…Kannan et al have recently reported promising results with Fe 3 O 4 NPs coated with 2-aminoterphthalic acid, ATA-IONPs, which provide sustained release of Fe 2+ ions in a pH-dependent manner. 140 Low pH favors the slow conversion of Fe 3+ to Fe 2+ , which activates ATS.…”

Green synthesis of iron oxide nanoparticles using Hibiscus rosa-sinensis for fortifying wheat biscuits

“…Iron, especially iron oxide or magnetite (Fe 3 O 4 ), nanoparticles are one of the most significant set of inorganic nanoparticles due to their super paramagnetism and easy separation [9]. Particle size to nanoscale, when reduced, exhibit increase in absorption when utilised for fortifying foods [10].…”

Porphyrin Derivative Nanoformulations for Therapy and Antiparasitic Agents

“…More recently, metal and metal oxide nanoparticles have also been explored as alternatives for antimalarial formulations. An interesting preclinical study using an artesunate formulation with iron oxide nanoparticles was reported by Kannan et al [151]. In this work, the nanosystem was designed for the sustained pH-dependent release of Fe 2+ ions within the parasitic food vacuole to induce a toxic ROS spurt.…”