中成药2025，Vol.47Issue(6)：1796-1804,9.DOI:10.3969/j.issn.1001-1528.2025.06.004
漆黄素纳米结构脂质载体制备及其体内药动学评价
Preparation of fisetin-loaded nanostructured lipid carriers and evaluation of their in vivo pharmacokinetics
摘要
Abstract
AIM To prepare fisetin-loaded nanostructured lipid carriers,and to evaluate their in vivo pharmacokinetics.METHODS Ethanol injection method was applied to preparing the nanostructured lipid carriers.With monostearin-phospholipid ratio,monostearin-triacetin ratio and D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)concentration as influencing factors,encapsulation efficiency as an evaluation index,the formulation was optimized by Box-Behnken response surface method.The crystal form was analyzed by X-ray powder diffraction,after which the morphology was observed by transmission electron microscopy,infrared spectroscopy analysis was performed,the drug relaese was investigated by dialysis bag method,and the stability was determined.Eighteen rats were randomly assigned into 3 groups and given intragastric administration of the 0.5％CMC-Na suspensions of fisetin and its phospholipid complex,nanostructured lipid carriers(150 mg/kg),respectively,after which blood collection was made at0.25,0.5,1,1.5,2,3,4,6,8,12 h,UPLC-MS/MS was adopted in the plasma concentration determination of fisetin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be 1.56∶1 for monostearin-phospholipid ratio,3.05∶1 for monostearin-triacetin ratio,and 0.2 mg/mL for TPGS concentration.The nearly round fisetin-loaded nanostructured lipid carriers demonstrated the average encapsulation efficiency,drug loading,particle size and Zeta potential of(86.14±1.28)％,(8.96±0.26)％,(212.35±9.04)nm and-(31.13±1.16)mV,respectively.Raw medicine existed in the nanostructured lipid carriers in an amorphous state,preparation process did not affect the hydrogen bonding between raw medicine and phospholipids.The nanostructured lipid carriers displayed the accumulative release rate of 46.12％within 3 h in simulated gastric juice,and that of about 50％within 18 h in simulated intestinal fluid,whose freeze-dried powder exhibited good stability after being placed for 6 months.Compared with raw medicine and phospholipids complex,the nanostructured lipid carriers displayed prolonged tmax,t1/2(P＜0.01)and increased Cmax,AUC0-t,AUC0-∞(P＜0.01),whose relative bioavailability was enhanced to 7.07 times.CONCLUSION Nanostructured lipid carriers can improve the oral bioavailability of fisetin.关键词
漆黄素/纳米结构脂质载体/制备/体内药动学/乙醇注入法/UPLC-MS/MSKey words
fisetin/nanostructured lipid carriers/preparation/in vivo pharmacokinetics/ethanol injection method/UPLC-MS/MS分类
药学引用本文复制引用
房伟,王奎鹏,韩德恩..漆黄素纳米结构脂质载体制备及其体内药动学评价[J].中成药,2025,47(6):1796-1804,9.基金项目
河南省高等学校重点科研项目(22A350007) （22A350007）
