在这项研究中，我们开发了一种新型的姜黄素和索拉非尼联合给药方法，使用自微乳化给药系统（SMEDDS），称为索拉非尼-姜黄素自微乳化给药系统（SOR-CUR-SMEDDS）。采用星点设计-效应面法优化制剂，并进行体外细胞实验来评估姜黄素和索拉非尼组合的递送率和抗肿瘤功效。 SOR-CUR-SMEDDS 表现出 13.48±0.61 nm 的小尺寸分布、0.228±0.05 的低多分散指数 (PDI) 和 - 12.4 mV 的负 zeta 电位 (ZP)。 SOR-CUR-SMEDDS 对 HepG2 细胞（人肝细胞癌细胞）的半数抑制浓度 (IC50) 姜黄素低 3 倍，索拉非尼低 5 倍。透射电子显微镜 (TEM) 和粒径检测证实 SOR-CUR-SMEDDS 液滴呈均匀圆形，且纳米乳液粒径在 10-20 nm 范围内。对 SMEDDS 进行表征，然后研究通过透析膜的体外药物释放。姜黄素在联合递送系统中释放更完全，在介质中7天内表现出最大的体外药物释放（79.20％），而索拉非尼在释放介质中的累积释放率较低，在7天内达到58.96％ 。体外药代动力学研究表明，当以 SMEDDS 给药时，索拉非尼（1239.88 倍）和姜黄素（3.64 倍）的口服生物利用度显着增加。这些发现表明，SMEDDS 制剂可以极大地增强药物溶解度、改善药物吸收并延长体内循环，从而提高索拉非尼和姜黄素的口服生物利用度。© 2024。控释协会。

In this study, we developed a novel co-administration of curcumin and sorafenib using a Self micro-emulsifying Drug Delivery System (SMEDDS) called Sorafenib-Curcumin Self micro-emulsifying Drug Delivery System (SOR-CUR-SMEDDS). The formulation was optimized using star point design-response surface methodology, and in vitro cellular experiments were conducted to evaluate the delivery ratio and anti-tumor efficacy of the curcumin and sorafenib combination. The SOR-CUR-SMEDDS exhibited a small size distribution of 13.48 ± 0.61 nm, low polydispersity index (PDI) of 0.228 ± 0.05, and negative zeta potential (ZP) of - 12.4 mV. The half maximal inhibitory concentration (IC50) of the SOR-CUR-SMEDDS was 3-fold lower for curcumin and 5-fold lower for sorafenib against HepG2 cells (human hepatocellular carcinoma cells). Transmission electron microscopy (TEM) and particle size detection confirmed that the SOR-CUR-SMEDDS droplets were uniformly round and within the nano-emulsion particle size range of 10-20 nm. The SMEDDS were characterized then studied for drug release in vitro via dialysis membranes. Curcumin was released more completely in the combined delivery system, showing the largest in vitro drug release (79.20%) within 7 days in the medium, while the cumulative release rate of sorafenib in the release medium was low, reaching 58.96% on the 7 day. In vitro pharmacokinetic study, it demonstrated a significant increase in oral bioavailability of sorafenib (1239.88-fold) and curcumin (3.64-fold) when administered in the SMEDDS. These findings suggest that the SMEDDS formulation can greatly enhance drug solubility, improve drug absorption and prolong circulation in vivo, leading to increased oral bioavailability of sorafenib and curcumin.© 2024. Controlled Release Society.