尽管乳腺癌有多种治疗方式，但它仍然是女性中诊断最多的癌症类型之一。最近对乳腺癌表观遗传学的研究揭示了各种 HDAC 酶表达水平的一些异常。今后，目前的工作需要配制和表征基于脂质聚合物的混合纳米颗粒（LPN）系统，用于递送表观遗传调节剂药物 Belinostat，以用于乳腺癌的临床应用。使用改进的热均质法制备的贝利诺他纳米颗粒的尺寸为 166.6 ± 19.95 nm，包封率为 94.5 ± 5.1%。两种不同乳腺癌细胞（4T1 和 MCF 7）中细胞毒性、细胞摄取和蛋白质表达的体外表征揭示了该制剂与 MCF 7 细胞中的游离药物相比的优越性。随后，使用药代动力学和生物分布研究分析了制剂在健康和乳腺癌异种移植动物体内的行为。结果显示，与游离药物相比，该制剂在荷瘤动物中的药代动力学参数有数倍改善，而在健康动物中未观察到药代动力学行为的差异，表明该制剂在乳腺肿瘤中的生物分布和特异性发生了改变。生物分布研究证实了这一点，生物分布研究显示 4 小时后，动物模型肿瘤组织中纳米颗粒制剂的吸收和保留提高了 20 倍。因此，所开发的 LPN 系统有潜力作为 Belinostat 的新型药物递送系统，与游离药物相比具有多种优势。

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 behaviour of the formulation in in vivo settings of healthy and breast cancer xenograft bearing animals was analyzed using pharmacokinetic and biodistribution studies. The results revealed that the formulation demonstrated multi-fold improvement in the pharmacokinetic parameters in tumor bearing animals when compared with the free drug while no difference in pharmacokinetic behaviour was observed in healthy animals indicating the altered biodistribution and specificity of the formulation in breast tumor. This was confirmed by the biodistribution studies exhibiting 20-fold improved uptake and retention of the nanoparticulate formulation in tumor tissues of the animal model at the end of 4 h. Thus, the developed LPN system holds potential to act as a novel drug delivery system for Belinostat with several advantages over the free drug.