Polyethyleneglycol-serine nanoparticles as a novel antidote for organophosphate poisoning: synthesis, characterization, in vitro and in vivo studies

Abstract

Acute organophosphate pesticide poisoning causes considerable worldwide mortality and morbidity. In this study, serine was attached to the polyethylene glycol-bisaldehyde (PEG) as a novel antidote for diazinon (DZ) poisoning. Serine and PEG were conjugated with a reductive amination reaction. PEG-serine NPs (PEG-NPs) were purified and their structure was analyzed by ¹H NMR, ¹³C NMR, IR, and particle size was determined via dynamic light scattering. In vitro studies, including hemolysis assay and cytotoxicity on SK-BR-3 and HFFF2 cell lines, were performed. In vivo studies of PEG-NPs were evaluated on DZ-exposed mice. PEG-NPs were administered (i.p.) 20 min after a single dose of DZ (LD₅₀; 166 mg/kg). Atropine (20 mg/kg, i.p.) with pralidoxime (20 mg/kg, i.p.) was used as the standard therapy compared to PEG-NPs. NMR and IR data confirmed that the conjugation of PEG to serine occurred successfully. The average NP size was 22.1 ± 1.8 nm. The hemolysis of the PEG-NPs was calculated at 0.867%, 50% inhibitory concentration (IC₅₀) was calculated 36 ± 4.5, and 41 ± 3.4 mg/mL on SK-BR-3 and HFFF2 cell lines, respectively. Percentage of surviving significantly improved by 12.5, 25, and 25% through the usage of PEG-NPs at doses of 100, 200, and 400 mg/kg, respectively, when compared with the DZ group. Cholinesterase enzyme activity, lipid peroxidation, and mitochondrial function significantly improved through PEG-NPs when compared with the DZ group. PEG conjugated serine is very biocompatible with low toxicity and can reduce the acute toxicity of DZ as a new combination therapy.

Keywords:

• Poisoning
• PEG-serine
• nanoparticle
• antidote
• diazinon
• cytotoxicity

Author contributions

Pedram ebrahimnejad, Ali Davoodi, Hamid Irannejad, and Hamidreza Mohammadi: synthesize the nanoparticles. Hamid Irannejad: ¹H NMR, ¹³C NMR, and IR. Pedram ebrahimnejad, Ali Davoodi, and Hamidreza Mohammadi: mouse experiments with nanoparticles. Pedram ebrahimnejad and Javad Akhtari: DSC and particle size measurement. Javad Akhtari: in vitro studies. Ali Davoodi and Hamidreza Mohammadi: in vivo studies. Ali Davoodi and Hamidreza Mohammadi: material preparation, data collection, and analysis. Pedram ebrahimnejad, Ali Davoodi, Hamid Irannejad, Javad Akhtari, and Hamidreza Mohammadi: critical review of manuscript and study supervision. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Mazandaran University of Medical Sciences, Sari, Iran [grant number 1155].