Schistosomiasis is a devastating endemic water born tropical disease caused by a parasitic flat worm of the genus Schistosoma. It is usually associated with poverty, causing significant levels of morbidity with irreversible pathology in vital organs that have a negative impact on the human socioeconomic status and quality of life (Abou-El-Naga, 2015). In 2012, 200,000 deaths were attributable to schistosomiasis alone in sub-Saharan Africa (WHO, 2012). In 2014, an estimated 3.3 million disability-adjusted life years (DALY) were estimated as the global schistosomiasis burden. This enormous value is similar to that of malaria and tuberculosis burdens (Hotez et al., 2014). School-age children (5-14 years) are the most vulnerable group to infection due to their habit of swimming in infected water. They usually present with anaemia, eosinophilia, malnutrition, stunting growth and decreased school performance (el Zawawy et al., 1995; WHO, 2020). Despite the considerable disease burden, so far there is no effective vaccine for this parasite, the intermediate host control program is not always easy to maintain and chemotherapy remains the idol for disease control (Abou-El-Naga, 2018). Mass chemotherapy is a term applied by the World Health Organization (WHO), where anti-helminthic drugs, either alone or in combination, are used as a public health tool. It is a cost-effective method to reduce morbidity and mortality secondary to Schistosoma infection (Richter, 2000). Praziquantel (PZQ) remains the only effective frontline drug to treat schistosomes and is currently characterized by its exclusive and extensive use that can promote the evolution of schistosomes with reduced drug sensitivity (Abou-El-Naga et al., 2019). Recently, the WHO reported that at least 290.8 million people required periodic preventive chemotherapy with PZQ (WHO, 2020). PZQ is a pyrazine-isoquinoline derivative, developed by Bayer in the 1970s. It is a broad-spectrum anti-helminthic drug used in the treatment of parasitic flat worms. PZQ tablets are large, oblong and contain 600 mg (mg) of the active ingredient. It can be considered as the main chemotherapeutic agent in the treatment of schistosome spp. achieving cure rates reaching 60-90% and rarely 100% cure when administrated in a single oral dose of 40–60 mg/kg against the adult stage. It is inexpensive, well tolerated, with only mild and transient side effects (Andrews, 1985; Vale et al., 2017).

Various hypotheses have been assumed regarding the mechanism of action of PZQ. The key event is disruption of intracellular Ca2+ homeostasis leading to rapid, sustained Ca2+ influx that cause tetanic muscle contractions and tegumental disruption with subsequent exposure of hidden antigens to the host immune response (Pax et al., 1978; Day et al., 1992; Kohn et al., 2001), or activation of Sm-TRPMPZQ leading to disturbance in Ca2+ homeostasis in schistosomes (Park et al., 2019). Additionally, it inhibits the uptake adenosine and uridine nucleotides by schistosomes from their host leading to the death of the worm. Another straight-forward explanation of PZQ schistosomicidal effects is the drug inserting itself into the tegument altering its permeability and fluidity (Angelucci et al., 2007; Lima et al., 1994).

Even with PZQ’ advantages, it is poorly soluble in water, with low oral bioavailability, bitter taste and of large sized tablets. All these disadvantages can make it difficult for patients to comply, especially the most vulnerable (Gönnert and Andrews, 1977).

From a parasitological point of view, the major drawbacks of PZQ include its inability to affect the juvenile and invasive stages, resulting in failure of treatment in the highly endemic areas in addition to reported emergence of PZQ-reduced sensitivity strains (Abou-El-Naga et al., 2021; Abou-El-Naga et al., 2019). PZQ shows a biphasic spectrum of activity against S. mansoni. It is noticeably effective against the invasive stage, is inactive against the immature juvenile stage and is fully active against the sexually mature adult stage, at six to seven weeks post infection (P.I.) (Sabah et al., 1986; Pica-Mattoccia and Cioli, 2004).

In S. mansoni, multidrug resistance (MDR) is one of the main challenges limiting the efficacy of anti-schistosomal drugs. MDR can protect schistosomes from drugs and toxic metabolites through efflux of metabolic toxins and drugs, primarily mediated by ATP binding cassette (ABC) transporters. Multiple ABC transporters are identified in S. mansoni namely SMDR1, SMDR2 (P-glycoproteins-like molecules) and multidrug resistance-associated proteins (SmMRP1). These transporters reduce the intracellular concentration of drugs and hinder their chemotherapeutic efficacy (Kasinathan and Greenberg, 2012). Juvenile schistosomes were reported to express 2.5-fold higher basal levels of SMDR2 and SmMRP1 than adults. This may explain the lack of efficacy of PZQ against this stage compared to adults (Kasinathan et al., 2010).

Recently, nanotechnology has been adopted to improve the efficacy of drugs by increasing the permeability of drugs through the absorptive membranes which leads to a reduction in the required drug dose. It preserves the host cells and therefore loaded drugs exert better therapeutic efficacy with improved selectivity and less toxicity. Solid Lipid Nanoparticles (SLNs) have emerged as promising drug nanocarriers. They are relatively non-toxic, have good biocompatibility, high bioavailability, possess biodegradable nature and high in-vivo tolerability compared to other polymeric nanoparticles. Moreover, SLNs showed better colloidal stability upon storage compared to liposomes and provided controlled drug release (Ibrahim et al., 2022).

In parasitic diseases, nanoscale drug delivery systems have already been applied in the treatment of several diseases as leishmaniasis (Gutiérrez et al., 2016) and toxoplasmosis (Abou-El-Naga et al., 2017), and in control of Biomphalaria snail vector of S. mansoni (Younis et al., 2023).

Regarding schistosomiasis, the use of nano-enable drug delivery systems provides new hope for improving the therapeutic efficacy of different drugs. Several researches studied the effect of nanotechnology in the delivery of drugs such as PZQ-encapsulated in liposomes (Frezza et al., 2013). SLNs loaded PZQ was also studied against schistosomiais (De saouza et al., 2014; Radwan et al., 2019; Andrad et al., 2019; Partridg et al., 2019; Tawfeek et al., 2019). Encapsulated niosomes were also studied to overcome the reduced sensitivity of the parasite (Amer et al., 2022). Celecoxib loaded in SLNs was also recently studied as a single oral dose against different developmental stages of S. mansoni (Ibrahim et al., 2022).

The aim of this study was to evaluate the therapeutic efficacy of PZQ-loaded SLNs against immature stages of experimental schistosomiasis mansoni. The efficacy of the nanoparticulate form of the drug on the adult stage was also evaluated.