G-Rb1

Toxoplasma gondii (T. gondii), a globally prevalent zoonotic parasite, infects nucleated cells in warm-blooded animals, posing major public health risks. Current treatments (sulfadiazine/pyrimethamine) for the widespread parasite T. gondii have poor cyst penetration and significant side effects. While the natural compound baicalein (BAI, C₁₅H₁₀O₅) shows potent anti-T. gondii activity, its low solubility and high toxicity limit therapeutic use. To overcome BAI's limitations, we engineered ginsenoside Rb1-based nanoparticles (GRb1/BAI NPs) via self-assembly, leveraging GRb1's dual role as a biocompatible carrier and therapeutic booster. The GRb1/BAI NPs exhibited favorable characteristics, including ease of preparation, optimal particle size (∼110 nm), stable zeta potential (-33.82 ± 0.85 mV), high encapsulation efficiency (94.67 %) and drug load (36.09 %), and smooth sustained-release properties. In vitro and in vivo assessments revealed that the GRb1/BAI NPs exhibited limited cytotoxicity within the tested concentration range. Furthermore, compared with 70.28 μM of free BAI, the reduced IC₅₀ value (41.53 μM) of GRb1/BAI NPs demonstrated enhanced drug potency and safety along with significant inhibition of intracellular T. gondii proliferation as determined by quantifying parasite burdens based on the 529 repetitive sequence (rep-529) gene standard curve. In vivo experiments further confirmed that GRb1/BAI NPs elicited more durable and protective effects against acute (RH strain) and chronic (PRU strain) toxoplasmosis with significantly prolonged survival time and notably reduced cysts numbers in mice brains. GRb1/BAI NPs show promise as novel anti-T. gondii agents by leveraging the carrier's therapeutic activity while using natural excipients, thereby avoiding toxicity risks from synthetic alternatives.