Abstract Hepatic carcinoma (HC) is one of the most prevalent cancers, ranked as the second most common cause of cancer-related deaths worldwide. Silymarin (SYL) has been reported for its anticarcinogenic activity against various types of cancer such as prostate, breast, ovary, colon, lung, bladder and liver. Due to poor solubility and low bioavailability SYL lacks satisfactory therapeutic value thus designing a suitable and effective delivery system of SYL can led to improved therapeutic potential. The present study was aimed to develop SYL-loaded dextrose (DEX) modified bilosomes for targeted delivery to HC cells. The DEX-modified bilosomes were prepared through thin-film hydration method and optimized employing Box Behnken design. The bilosomes were evaluated for percent entrapment, drug loading, in vitro release and cytotoxicity on Hep-G2 cells. The optimized DEX-SYL-BL exhibited a particle size of 219.3 ± 2.99 nm, percent entrapment of 62.32 ± 4.23%, drug loading of 34.56 ± 1.23% and 84.96 ± 2.76% drug release respectively over a period of 24 hr. The stability of bilosomes was ascertained in simulated gastric and intestinal fluids. Cytotoxicity studies revealed greater performance of DEX-SYL-BL in terms of reduced viability in Hep-G2 cell lines when compared with pure SYL and SYL-BL. Further DEX-modified bilosomes were evaluated in vivo for their therapeutic efficacy in DEN-induced (Diethylnitrosamine) hepatic carcinoma in animal model. The DEX-SYL-BL displayed higher therapeutic potential as revealed from enhanced survival and reduced tumour burden in animals. DEX-SYL-BL also displayed significant restoration of altered oxidative markers and SGOT, SGPT levels towards normal value when compared with pure SYL.

中文翻译：

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用于经口给药的葡萄糖修饰的胆囊体：提高水飞蓟素在二乙基亚硝胺诱导的大鼠肝癌中的治疗潜力和稳定性。

摘要 肝癌 (HC) 是最普遍的癌症之一，在全球癌症相关死亡中排名第二。据报道，水飞蓟素 (SYL) 具有抗癌活性，可对抗各种类型的癌症，例如前列腺癌、乳腺癌、卵巢癌、结肠癌、肺癌、膀胱癌和肝癌。由于溶解性差和生物利用度低，SYL 缺乏令人满意的治疗价值，因此设计合适且有效的 SYL 递送系统可以提高治疗潜力。本研究旨在开发装载 SYL 的葡萄糖 (DEX) 修饰的胆汁体，用于靶向递送至 HC 细胞。通过薄膜水化法制备 DEX 修饰的胆囊体，并采用 Box Behnken 设计进行优化。评估了双糖体的截留百分比、载药量、体外释放和对 Hep-G2 细胞的细胞毒性。优化后的 DEX-SYL-BL 的粒径为 219.3 ± 2.99 nm，截留率为 62.32 ± 4.23%，载药量分别为 34.56 ± 1.23% 和 84.96 ± 2.76%，24 小时内药物释放。在模拟的胃液和肠液中确定了胆汁体的稳定性。细胞毒性研究表明，与纯 SYL 和 SYL-BL 相比，DEX-SYL-BL 在降低 Hep-G2 细胞系活力方面的性能更好。进一步在体内评估了 DEX 修饰的胆汁体在动物模型中对 DEN 诱导的（二乙基亚硝胺）肝癌的治疗效果。DEX-SYL-BL 显示出更高的治疗潜力，这从提高动物的存活率和减少肿瘤负担中可以看出。DEX-SYL-BL 还显示出改变的氧化标志物和 SGOT 的显着恢复，