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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  1 H NMR,  13  C 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 (LD 50 ; 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 (IC 50 ) 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.

drug and chemical toxicology

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