肝细胞癌(HCC)是全球癌症相关死亡的第三大原因。目前的治疗策略包括手术切除,肝移植,肝定向治疗,和全身治疗。索拉非尼(Sor)是美国食品和药物管理局(FDA)批准的第一个用于HCC治疗的全身性药物。然而,Sor的常规口服给药存在几个局限性:溶解度差,低生物利用度,耐药性的发展,和脱靶组织积聚,导致许多不利影响。纳米乳液,纳米递送系统,是水溶性差的药物的可行载体。它旨在提高药物的生物利用度,靶器官积累,减少脱靶组织暴露,从而改善治疗结果,同时尽量减少副作用。本研究使用均质化技术配制了Sor纳米乳液(SorNanoEm)。所得纳米乳液的特征在于粒径(121.75±12nm),多分散指数(PDI;0.310),zeta电位(-12.33±1.34mV),粘度(34,776±3276CPs),pH值(4.38±0.3)。透射电子显微镜显示球形纳米液滴,没有聚集迹象表明稳定性。此外,将Sor封装在纳米乳液中持续释放,有可能降低治疗剂量的频率。对HepG2细胞系的细胞毒性评估显示,与Sor悬浮液相比,SorNanoEm具有显著(P<0.05)更有效的细胞毒性作用。随后的测试强调了SorNanoEm在小鼠中的优异的药代动力学参数和降低的剂量要求。它表现出增强的安全性,特别是在行为上,大脑,还有肝脏,与它的悬浮形式相比。这些发现强调了Sor纳米乳液增强的药理和毒理学属性,提示其在肝癌治疗中的潜在效用。
Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths worldwide. Current treatment strategies include surgical resection, liver transplantation, liver-directed therapy, and systemic therapy. Sorafenib (Sor) is the first systemic drug authorized by the US Food and Drug Administration (FDA) for HCC treatment. Nevertheless, the conventional oral administration of Sor presents several limitations: poor solubility, low bioavailability, drug resistance development, and off-target tissue accumulation, leading to numerous adverse effects. Nano-emulsion, a nano-delivery system, is a viable carrier for poorly water-soluble drugs. It aims to enhance drug bioavailability, target organ accumulation, and reduce off-target tissue exposure, thus improving therapeutic outcomes while minimizing side effects. This study formulated Sor nano-emulsion (Sor NanoEm) using the homogenization technique. The resultant nano-emulsion was characterized by particle size (121.75 ± 12 nm), polydispersity index (PDI; 0.310), zeta potential (-12.33 ± 1.34 mV), viscosity (34,776 ± 3276 CPs), and pH (4.38 ± 0.3). Transmission Electron Microscopy exhibited spherical nano-droplets with no aggregation signs indicating stability. Furthermore, the encapsulation of Sor within the nano-emulsion sustained its release, potentially reducing the frequency of therapeutic doses. Cytotoxicity assessments on the HepG2 cell line revealed that Sor NanoEm had a significantly (P < 0.05) more potent cytotoxic effect compared to Sor suspension. Subsequent tests highlighted superior pharmacokinetic parameters and reduced dosage requirements of Sor NanoEm in mice. It exhibited an enhanced safety profile, particularly in behavior, brain, and liver, compared to its suspended form. These findings underscore the enhanced pharmacological and toxicological attributes of Sor Nano-emulsion, suggesting its potential utility in HCC treatment.