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Despite various treatment modalities for breast cancer, it still persists as one of the most diagnosed types of cancer in females. The recent investigations in the epigenetics of breast cancer reveal several aberrations in the expression levels of various HDAC enzymes. Henceforth, the present work entails the formulation and characterization of a lipid polymer-based hybrid nanoparticulate (LPN) system for delivery of an epigenetic modulator drug, Belinostat, for its clinical application in breast cancer. The size of Belinostat nanoparticles prepared using a modified hot homogenization method was found to be 166.6 ± 19.95 nm with an encapsulation efficiency of 94.5 ± 5.1%. In vitro characterization for cytotoxicity, cellular uptake, and protein expression in two different breast cancer cells, 4T1 and MCF 7, revealed the superiority of the formulation in comparison with the free drug in MCF 7 cells. Subsequently, the …