Contents lists available at ScienceDirect Journal of Drug Delivery Science and Technology journal homepage: www.elsevier.com/locate/jddst Curcumin loaded nanoparticles reversed monocrotophos induced motor impairment and memory deficit: Role of oxidative stress and intracellular calcium level Mukesh Mandal, Pawan Jaiswal, Awanish Mishra * Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Raebareli (NIPER-R), Bijnor-Sisendi Road, Sarojini Nagar, Near CRPF Base Camp, Lucknow, UP, 226002, India ARTICLE INFO Keywords: Organophosphorus Monocrotophos Curcumin nanoparticles Neurotoxicity Oxidative stress Intracellular Ca 2+ level ABSTRACT Monocrotophos is one of the extensively used organophosphorus insecticides in agriculture and animal hus- bandry in India. It induces neurotoxicity by inhibiting acetyl cholinesterase enzyme and elevating oxidative stress. Curcumin, dietary polyphenol, well known for its antioxidant and anti-inflammatory properties which could elicit protective effect against monocrotophos induced neurobehavioural abnormalities. Therefore this study is aimed to investigate ameliorative effect of curcumin loaded Nanoparticles on monocrotophos induced neurotoxicity. Curcumin loaded PLGA nanoformulation was prepared using nanoprecipitation technique and was char- acterized using zeta sizer, FTIR and NMR spectroscopy. For in-vivo study, 30 male rats were utilized. Exposure of monocrotophos was done at 2 mg/kg (p.o.) for 28 days. Curcumin bulk and cucurmin loaded Nanoparticles were administered with or without monocrotophos. Effect of monocrotophos exposure on behavioural changes was assessed by analysing spontaneous locomotor activity, motor coordination in rotarod test and contextual fear memory in passive shock avoidance paradigm. Effect on biochemical alteration in blood and brain were esti- mated. The average particle size of Curcumin loaded Nanoparticles was 114.9 nm and in-vitro release study suggested suitable release of Curcumin in simulated intestinal fluid. Results of in-vivo study indicated, monocrotophos exposure caused a significant increase in reactive oxygen species, thiobarbituric acid reactive substances, and intracellular free calcium levels along with altered behavioural abnormalities in locomotor activity, motor co- ordination, learning and memory. Decline in antioxidant defence level might suggest reduced host defence response. Treatment with curcumin alone did not significantly reversed monocrotophos induced neurotoxicity in rats. Whilst, treatment with curcumin loaded nanoparticles significantly reduced monocrotophos induced be- havioural and biochemical alteration in rat brain. The outcome of the present study suggested improved efficacy of curcumin loaded nanoparticles, possibly via its enhanced bioavailability. Further alleviation of oxidative stress and intracellular free Ca 2+ level might be speculated as one of the plausible neuroprotective mechanism of curcumin in this study. 1. Introduction In the rapidly developing world, people are continuously being exposed to numerous environmental pollutants such as industrial waste, polluted air, heavy metals, pesticides etc. which increases health care concerns. Pesticides and insecticides are very important group of environmental pollutants used in intensive agriculture for protection against diseases and pests [1]. According to the Food and Agricultural Organization and World Health Organization (WHO), most of the or- ganophosphorus (phorate, dimethoate, monocrotophos etc.) have been banned in different countries including India. Monocrotophos, an or- ganophosphate pesticide, is extensively being used in Indian agri- cultural segment due to its ease of availability and widely preferred due to cheaper price [2]. According to the toxicology data network, human and animal ex- posure to monocrotophos, has been reported through dermal, https://doi.org/10.1016/j.jddst.2020.101559 Received 18 December 2019; Received in revised form 23 January 2020; Accepted 30 January 2020 * Corresponding author. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER-R), Bijnor-Sisendi Road, Sarojini Nagar, Near CRPF Base Camp, Lucknow, 226002, UP, India. E-mail addresses: awanish1985@gmail.com, awanish1985@gmail.com (A. Mishra). Journal of Drug Delivery Science and Technology 56 (2020) 101559 Available online 03 February 2020 1773-2247/ © 2020 Elsevier B.V. All rights reserved. T