Enhancing MS‐275 Anticancer Activity: Encapsulation of MS‐275 in TPGS Micelles Demonstrated High Efficiency

Abstract

MS‐275, a histone deacetylase inhibitor, has proven anticancer activities against various malignancies. However, its clinical application has been constrained by dose‐limiting toxicity, off‐target effects, and variable clinical outcomes. Clinical data suggest that sustained low MS‐275 doses could achieve a more selective and consistent effect. This study aimed at enhancing the anticancer activity of MS‐275 by encapsulating it in D‐α‐tocopheryl polyethylene glycol 1000 succinate (TPGS) micelles. The produced nanoformulations were characterized by their low polydispersity (0.201), negative zeta potential (−0.397 mV), and high entrapment efficiency (98.8%). Experimental evaluation of the formulation showed a significant reduction in HepG2, HCT116, and MCF7 cells’ viability, associated with enhanced apoptosis at a lower IC50 compared to MS‐275 alone. The formulation was further examined on cancer cells xenografted on the chorioallantoic membrane (CAM) of chick embryos. The results showed a substantial reduction in tumor size. TPGS micelles alone induced an accumulation in G1 and slightly reduced the cellular viability of the examined cell lines. Our results suggest that encapsulating MS‐275 in TPGS micelles represents a promising strategy to enhance MS‐275 therapeutic impact while minimizing its pharmacological dosage.