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.