Spiramycin-loaded maltodextrin nanoparticles as a promising treatment of toxoplasmosis on murine model

Abstract

Despite being the initial choice for treating toxoplasmosis, sulfadiazine and pyrimethamine have limited effectiveness in eliminating the infection and were linked to a variety of adverse effects. Therefore, the search for new effective therapeutic strategies against toxoplasmosis is still required. The current work is the first research to assess the efficacy of spiramycin-loaded maltodextrin nanoparticles (SPM-loaded MNPs) as a novel alternative drug therapy against toxoplasmosis in a murine model. Fifty laboratory-bred Swiss albino mice were divided into five groups: normal control group (GI, n = 10), positive control group (GII, n = 10), orally treated with spiramycin (SPM) alone (GIII, n = 10), intranasal treated with SPM-loaded MNPs (GIV, n = 10), and orally treated with SPM-loaded MNPs (GV, n = 10). Cysts of Toxoplasma gondii ME-49 strain were used to infect the mice. Tested drugs were administered 2 months after the infection. Drug efficacy was assessed by counting brain cysts, histopathological examination, and measures of serum CD19 by flow cytometer. The orally treated group with SPM-loaded MNPs (GV) showed a marked reduction of brain cyst count (88.7%), histopathological improvement changes, and an increasing mean level of CD19 (80.2%) with significant differences. SPM-loaded MNPs showed potent therapeutic effects against chronic toxoplasmosis. Further research should be conducted to assess it in the treatment of human toxoplasmosis, especially during pregnancy.

Keywords: Maltodextrin nanoparticles; Spiramycin; Toxoplasmosis; Treatment.

Fig. 1

Mortality rate in the studied groups

Fig. 2

Cross sections of the brain (A, B, C, D). A Brain sections of the positive control group showed severe inflammatory reaction (yellow arrow) and severe neurodegenerative changes (red arrow) (H&E × 100). B SPM alone orally treated group (GIII) showed severe neurodegenerative changes (red arrow), severe vasculitis (circles), and apoptotic figures (stars) (H&E × 200). C SPM-loaded MNPs orally treated group (GV) showed mild inflammatory infiltration of mononuclear cells (lymphocytes), mild gliosis, mild neurodegenerative changes (red arrow), and mild vasculitis (circles) (H&E × 100). D SPM-loaded MNPs orally treated group (GV) high power showed edema (black arrow) and mild vasculitis (circles) (H&E × 200)

Fig. 3

Cross sections of liver (A, B, C, D). A Normal liver section. B Liver sections of the positive control group showed vascular congestion, moderate portal inflammation and necrosis (red arrow). C SPM alone orally treated group (GIII) showed mild presence of portal inflammation (red arrow) and severe central vein necrosis and inflammation (yellow arrow). D SPM-loaded MNPs orally treated group (GV) showed moderate presence of portal inflammation (red arrow) and severe central vein necrosis and inflammation (yellow arrow) (H&E × 200).

Fig. 4

Cross sections of spleen (A, B, C, D). A Section of normal splenic follicles. B The positive control group showed atrophy of white pulp, fusion of follicles, and congestion of red pulp (red arrow). C SPM-loaded MNPs nasally treated group showed mild atrophy of white pulp and mild congestion of red pulp. D SPM-loaded MNPs orally treated group showed mild atrophy of white pulp and severe congestion of red pulp (yellow arrow) (H&E ×200).

Fig. 5

Histograms of logarithmic dot plots present the lymphocyte population and gating that was performed on the CD19-positive cells of samples of the different studied groups