The potential of niosome-encapsulated sage extract in reducing the activity of the Toxoplasma gondii parasite

Background The tachyzoite is the active, fast-replicating stage of Toxoplasma gondii , causing tissue damage. Treatments like pyrimethamine and sulfadiazine target this stage, but their efficacy is limited due to the parasite's ability to form resistant tissue cysts, requiring advanced strategies to address both stages. Objectives Sage extract-loaded niosomes were prepared, and their properties and drug delivery efficiency were tested. Normal and parasite cells were exposed to free sage extract, niosome-encapsulated sage extract, clindamycin, and the synergistic niosome-drug combination. Subsequently, parasite load, cell viability, and toxicity were assessed using the MTT assay, along with an independent analysis of apoptosis induction for both normal and parasite cells. Parasite load was assessed by measuring cycle threshold (CT) values using real-time quantitative PCR (qPCR) to track tachyzoite counts on days 0, 3, 6, and 10. Results The prepared niosomes showed high encapsulation efficiency and active substance release. HeLa and Vero cell viability slightly decreased with treatment. Apoptosis rates in HeLa cells were 3.3% ± 2.1 (free extract), 5.4% ± 1.4 (niosome-loaded extract), and 6% ± 1.2 (synergistic combination). Despite high toxicity to parasite cells, apoptosis in HeLa cells was unaffected. The viability of the parasite decreased progressively with increasing concentrations of the therapeutic compounds. The synergistic combination demonstrated the highest toxicity (100% toxicity at 32 mg/mol), followed by clindamycin and niosome-encapsulated sage extract (100% toxicity at 256 mg/mol), while the free sage extract was the least effective (74% toxicity at the highest concentration). The EC50 values were as follows: clindamycin (3.86 mg/ml), free sage extract (32.3 mg/ml), and niosome-encapsulated sage extract (3.99 mg/ml). The results of the quantitative molecular evaluation indicated that all the therapeutic compounds under investigation affected the parasite load over time. Conclusions In general, all therapeutic compounds were effective in reducing parasite load over time, especially when compared with the control group. All the therapeutic compounds under trial had a certain effect in eradicating tachyzoites. The synergistic compound was the most effective. Niosome-encapsulated sage extract was the most stable and effective according to statistical analysis of the data. The study needs further studies to support the results and consider them in clinical application.