ArticleDaru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences2026
TPGS-stabilized pyrimethamine micelles promote ROS-associated apoptosis in MDA-MB-231 cells and suppress tumour progression in a murine lymphoma model.
Article in Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundA dihydrofolate reductase inhibitor, pyrimethamine has an emerging anticancer potential but is not well soluble in aqueous and bioavailable. The D-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)-based micellar nanoformulation was developed to overcome these challenges to improve its therapeutic performance.
objectiveThe D-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)-based micellar nanoformulation was developed to overcome these challenges to improve its therapeutic performance.
methodsTPGS micelles containing pyrimethamine were developed through solvent casting-rehydration and studied through DLS, AFM, SEM and TEM.
resultsThe maximally efficient expression generated homogeneous spherical micelles with an average diameter of about 74 nm and a low polydispersity (0.20) that is very homogeneous and stable. Persistent bi-phasic drug delivery was seen in physiological conditions. TPGS-Stabilized Pyrimethamine Micelles Promote ROS-Associated Apoptosis. In MDA-MB-231 breast cancer cells, the nanoformulation increased cytotoxicity and intracellular uptake compared with free pyrimethamine. The experiment showed that in mechanistic studies, there was high production of reactive oxygen species, high Annexin V-positive populations of apoptotic cells and G2/M phase arrest, which were associated with increased ROS generation, apoptosis, and cell-cycle arrest. In the murine lymphoma model, the nanoformulation reduced tumour progression and resulted in 100% survival through Day 30.
conclusionThese findings support further preclinical investigation of TPGS-based pyrimethamine micelles as a potential anticancer delivery strategy. Additional studies are required to confirm their mechanism, pharmacokinetic behaviour, long-term safety, and efficacy in breast-cancer-specific animal models.
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