Center for Nano Drug/Gene Delivery and Tissue Engineering, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, China.
Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, No.301, Xuefu Road, Jingkou District, Zhenjiang City, 212013, Jiangsu Province, China.
AAPS PharmSciTech. 2019 Feb 4;20(3):98. doi: 10.1208/s12249-019-1290-6.
In this study, syringic acid-loaded TPGS liposome (SA-TPGS-Ls) was successfully prepared to improve oral bioavailability of syringic acid (SA). SA is a natural and notable antioxidant activity compound with its limited bioavailability ascribable to its poor aqueous solubility and fast elimination. Recently, TPGS has become a perfect molecular biomaterial in developing several carrier systems with sustained, controlled, and targeted the drug delivery. SA-TPGS-Ls was prepared via thin-film dispersion method and characterized in terms of particle size, stability, morphology, and encapsulation efficiency (EE). The results showed that SA-TPGS-Ls had regular spherical-shaped nanoparticles with EE of 96.48 ± 0.76%. The pharmacokinetic studies demonstrated a delayed MRT and prolonged t, while relative oral bioavailability increased by 2.8 times. Tissue distribution showed that SA-TPGS-Ls maintained liver drug concentration while delayed elimination was also observed in the kidney. In CCl-induced hepatotoxicity study, the activities of hepatic T-AOC, GSH-Px, CAT, GSH, and SOD were greatly elevated, while serum biological markers ALT, AST, and AKP were reduced after treatment of mice with SA-TPGS-Ls. Histopathological studies confirmed that SA-TPGS-Ls could remarkably improve the status of hepatic tissues. Collectively, SA-TPGS-Ls significantly improved the drug encapsulation efficiency, stability coupled with bioavailability of SA, hence increasing in vivo antioxidant activity of the drug.
在这项研究中，成功制备了负载丁香酸的 TPGS 脂质体（SA-TPGS-Ls），以提高丁香酸（SA）的口服生物利用度。SA 是一种天然的、具有显著抗氧化活性的化合物，但其生物利用度有限，这归因于其较差的水溶性和快速消除。最近，TPGS 已成为开发具有持续、控制和靶向药物递送的几种载体系统的理想分子生物材料。SA-TPGS-Ls 通过薄膜分散法制备，并从粒径、稳定性、形态和包封效率（EE）等方面进行了表征。结果表明，SA-TPGS-Ls 具有规则的球形纳米粒子，EE 为 96.48±0.76%。药代动力学研究表明，MRT 延迟，t 延长，相对口服生物利用度增加 2.8 倍。组织分布表明，SA-TPGS-Ls 保持了肝脏的药物浓度，同时在肾脏中也观察到了消除的延迟。在 CCl 诱导的肝毒性研究中，SA-TPGS-Ls 处理后的小鼠肝组织 T-AOC、GSH-Px、CAT、GSH 和 SOD 的活性大大提高，而血清生物标志物 ALT、AST 和 AKP 则降低。组织病理学研究证实，SA-TPGS-Ls 可以显著改善肝组织的状况。总之，SA-TPGS-Ls 显著提高了 SA 的药物包封效率、稳定性和生物利用度，从而提高了药物的体内抗氧化活性。
