Toxoplasma gondii is an intracellular protozoan parasite of worldwide distribution that can infect nearly all worm-blooded hosts including human. It is characterized by an acute phase of rapidly replicating tachyzoites with nearly no or little symptoms in immunocompetent hosts followed by a chronic phase with cysts in tissues especially in the immune-privileged organs as the brain. Although it was believed that chronic toxoplasmosis has no clinical impact on the hosts, a lot of neuropsychiatric problems have been linked with chronic toxoplasmosis in the last decades. Schizophrenia, manic-depressive disorder, obsessive–compulsive disorder, Alzheimer disease, cryptogenic epilepsy and increased suicide attempts are all among the neuropsychiatric problems that were associated with latent toxoplasmosis (Dalimi and Abdoli 2012).

Till now, no treatment is available for the dormant Toxoplasma tissue cyst as it is highly resistant to most of the known anti-Toxoplasma therapeutic modalities. Although the treatment of choice in toxoplasmosis is the combination of pyrimethamine and sulfadiazine, it is still showing no satisfactory results against tissue cysts in chronic toxoplasmosis in addition to its severe side effects and the emergence of pyrimethamine and sulfadiazine resistant strains (Konstantinovic et al., 2019). Thus, an urgent need for a safe effective drug that can cross the blood brain barrier and affect the cysts in the brain has been emerged.

Guanabenz, which is FDA-approved alpha-2-adrenergic receptor agonist antihypertensive drug showed promising results in clinical researches for treatment of many diseases as cystic fibrosis (Norez et al., 2008) and Amyotrophic lateral sclerosis (Bella et al., 2017). Moreover, it showed a significant antiamoebic activity against both Acanthamoeba castellanii and Naegleria fowleri when it was conjugated to gold and silver nanoparticles (Anwar et al., 2019). Benmerzouga et al. (2015) studied the effect of guanabenz on Toxoplasma and showed a remarkable effect in the treatment of acute toxoplasmosis in addition to its ability to reduce the number of the brain tissue cysts although it could not completely eradicate them.

Nanoparticles have many advantages that enable them to be used as drug delivery systems to increase the drug bioavailability, deliver smaller dose of the drug with the same therapeutic results but with less toxicity, extend the drug circulation half-life, increase drug concentration at the target tissue beside its high drug loading capacity and controlled drug release and the ability to cross biological barriers as blood brain barrier resulting in a significant improvement in the drug concentration in the brain (Pal et al. 2011; Gowda et al., 2013; Zhang et al., 2016). Poly lactic-co-glycolic acid (PLGA) belongs to a family of FDA-approved biodegradable polymers which is commonly used as drug delivery vehicle due to its favorable degradation characteristics and possibilities for sustained drug delivery (Makadia and Siegel., 2011), however, its poor water stability may result in rapid clearance of the nanoparticles in vivo. Therefore, the chemical conjugation of polyethylene glycol (PEG) with PLGA can enhance the biological half-life of PLGA nanoparticles and improve its incorporation with either hydrophobic or hydrophilic drugs for controlled drug release (Khaledi et al., 2020).

So, incorporation of guanabenz with polyethylene glycol Poly lactic-co-glycolic acid (PEG-PLGA) nanoparticles was tested to evaluate its efficacy against chronic experimental toxoplasmosis.