Febuxostat (FBX) is a drug able to inhibit xanthine oxidase and reduce uric acid production commonly used for the treatment of hyperuricemia in subjects suffering from gout. Several studies have also been directed at its use as anti-cancer drug during the last years, opening a window for its off-label use. In the present study, an optimized formulation in terms of vesicle size and drug release, obtained by encapsulation of FBX into the emulsomes (FBX-EMLs), was evaluated for its cytotoxic potential in human colorectal carcinoma (HCT 116) cells. The optimized FBX-EMLs formula had an improved half maximal inhibitory concentration (IC50), about 4-fold lower, compared to the free drug. The cell cycle analysis showed a significant inhibition of the HCT 116 cells proliferation following FBX-EMLs treatment compared to all the other conditions, with a higher number of cells accumulating on G2/M and pre-G1 phases, paralleled by a significant reduction of cells in G0/G1 and S phases. The optimized formula was also able to significantly increase the percentage of cell population in both early and late stages of apoptosis, characterized by a higher intracellular caspase-3 concentration, as well as percentage of necrotic cells. Lastly, the FBX ability to decrease the mitochondrial membrane potential was enhanced when the drug was delivered into the EMLs. In conclusion, the new formulation of FBX into EMLs improved all the parameters related to the anti-proliferative activity and the toxic potential of the drug towards colorectal cancer cells.

中文翻译：

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将非布索坦封装到乳剂中可显着增强该药物对 HCT 116 结肠癌细胞的细胞毒性潜力


非布索坦（FBX）是一种能够抑制黄嘌呤氧化酶并减少尿酸产生的药物，通常用于治疗痛风患者的高尿酸血症。过去几年中，多项研究还针对其作为抗癌药物的用途，为其超说明书使用打开了窗口。在本研究中，通过将 FBX 封装到乳剂 (FBX-EML) 中获得了囊泡大小和药物释放方面的优化制剂，并评估了其在人结直肠癌 (HCT 116) 细胞中的细胞毒性潜力。优化的 FBX-EML 配方具有改进的半数抑制浓度 (IC50)，与游离药物相比降低约 4 倍。细胞周期分析显示，与所有其他条件相比，FBX-EML 处理后 HCT 116 细胞增殖受到显着抑制，G2/M 和前 G1 期的细胞数量增多，同时细胞数量显着减少在G0/G1和S阶段。优化的配方还能够显着增加细胞凋亡早期和晚期的细胞群百分比，其特点是细胞内 caspase-3 浓度更高，以及坏死细胞的百分比。最后，当药物被输送到 EML 中时，FBX 降低线粒体膜电位的能力得到增强。总之，将 FBX 加入 EML 中的新配方改善了与抗增殖活性和药物对结直肠癌细胞的潜在毒性相关的所有参数。