自我微乳剂药物递送系统（SMEDDS）在索拉非尼与姜黄素联用中的开发与优化
Development and optimization of a self micro-emulsifying drug delivery system (SMEDDS) for co-administration of sorafenib and curcumin
影响因子:5.50000
分区:医学3区 / 医学：研究与实验3区 药学3区
发表日期:2025 May
作者:
Xingzhen Huang, Lizhen Feng, Xuefang Lu, Fan Yang, Shengjun Liu, Xueqian Wei, Jinping Huang, Yao Wang, Dongyi Huang, Tingting Huang
摘要
本研究开发了一种新型的姜黄素与索拉非尼联用的自我微乳剂药物递送系统（SMEDDS），命名为索拉非尼-姜黄素自我微乳剂系统（SOR-CUR-SMEDDS）。采用星点设计-响应面法对制剂进行优化，并通过体外细胞实验评估姜黄素和索拉非尼组合的递送比例及抗肿瘤效果。结果显示，SOR-CUR-SMEDDS具有粒径13.48 ± 0.61纳米、低多分散指数（PDI）0.228 ± 0.05和负的Zeta电位（-12.4毫伏）。在HepG2（人肝细胞癌）细胞中，SOR-CUR-SMEDDS的半数抑制浓度（IC50）比单独姜黄素低3倍，比索拉非尼低5倍。透射电子显微镜（TEM）和粒径检测确认，SOR-CUR-SMEDDS的液滴均匀圆形，粒径在10-20纳米范围内。对其药物释放在体外通过透析膜进行研究，发现姜黄素在联合递送系统中的释放更完全，在7天内释放最大（79.20%），而索拉非尼的累计释放率较低，在第7天达58.96%。体外药代动力学研究表明，SMEDDS显著提高索拉非尼（1239.88倍）和姜黄素（3.64倍）的口服生物利用度。上述结果表明，SMEDDS制剂能大幅增强药物溶解度，改善药物吸收并延长体内循环时间，从而提升索拉非尼和姜黄素的口服生物利用度。
Abstract
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.