Key Lab for Drug Delivery & Tissue Regeneration, Jiangsu Provincial Research Center for Medicinal Function Development of New Food Resources, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, People's Republic of China.
School of Chemistry and Chemical Engineering, Yancheng Institute of Technology, Yancheng, 224003, Jiangsu, China.
AAPS PharmSciTech. 2021 Jan 13;22(1):45. doi: 10.1208/s12249-020-01901-y.
This study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the solubility, oral bioavailability, and hypolipidemic effects of syringic acid (SA), a bioactive and poorly-soluble polyphenol. Based on the response surface methodology-central composite design (RSM-CCD), an optimum formulation of SA-SMEDDS, consisting of ethyl oleate (oil, 12.30%), Cremophor-EL (surfactant, 66.25%), 1,2-propanediol (cosurfactant, 21.44%), and drug loading (50 mg/g), was obtained. The droplets of SA-SMEDDS were nanosized (16.38 ± 0.12 nm), spherically shaped, and homogeneously distributed (PDI = 0.058 ± 0.013) nanoparticles with high encapsulation efficiency (98.04 ± 1.39%) and stability. In vitro release study demonstrated a prolonged and controlled release of SA from SMEDDS. In vitro cell studies signified that SA-SMEDDS droplets substantially promoted cellular internalization. In comparison with the SA suspension, SA-SMEDDS showed significant prolonged T, t, and MRT after oral administration. Also, SA-SMEDDS exhibited a delayed in vivo elimination, increased bioavailability (2.1-fold), and enhanced liver accumulation. Furthermore, SA-SMEDDS demonstrated significant improvement in alleviating serum lipid profiles and hepatic steatosis in high-fat diet-induced hyperlipidemia in mice. Collectively, SMEDDS demonstrated potential as a nanosystem for the oral delivery of SA with enhanced bioavailability and hypolipidemic effects.
本研究旨在开发一种自微乳药物传递系统（SMEDDS），以提高原儿茶酸（SA）的溶解度、口服生物利用度和降血脂作用。SA 是一种生物活性和难溶性多酚。基于响应面法-中心复合设计（RSM-CCD），得到了 SA-SMEDDS 的最佳配方，由油酸乙酯（油，12.30%）、吐温-80（表面活性剂，66.25%）、1,2-丙二醇（助表面活性剂，21.44%）和药物载量（50mg/g）组成。SA-SMEDDS 的液滴为纳米级（16.38±0.12nm）、球形、均匀分布（PDI=0.058±0.013）的纳米粒，具有高包封效率（98.04±1.39%）和稳定性。体外释放研究表明，SMEDDS 能延长和控制 SA 的释放。体外细胞研究表明，SA-SMEDDS 液滴能显著促进细胞内化。与 SA 混悬液相比，SA-SMEDDS 口服后 T、t 和 MRT 显著延长。此外，SA-SMEDDS 表现出体内消除延迟、生物利用度增加（2.1 倍）和肝脏蓄积增加。此外，SA-SMEDDS 还能显著改善高脂饮食诱导的高血脂症小鼠的血清脂质谱和肝脂肪变性。总之，SMEDDS 作为一种口服传递 SA 的纳米系统具有增强生物利用度和降血脂作用的潜力。
