ω-3多不饱和脂肪酸甘油酯纳米乳的制备及其在肝损伤治疗中的应用  

Preparation of Omage-3 Polyunsaturated Fatty Acid Glyceride Nanoemulsion and Its Application in the Treatment of Liver Injury

作　　者：韩雯雯 李耀威 张馨欣 HAN Wenwen;LI Yaowei;ZHANG Xinxin(School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing 210023;Shanghai Institute of Materia Medical,Chinese Academy of Sciences,Shanghai 201203)

机构地区：[1]南京中医药大学新中药学院,江苏南京210023 [2]中国科学院上海药物研究所,上海201203

出　　处：《中国医药工业杂志》2024年第9期1220-1228,共9页Chinese Journal of Pharmaceuticals

基　　金：国家自然科学基金(82222066);国家药典委药品标准制修订课题(2021Y19、2022Y30);国家药品监督管理局化学药品制剂质量分析重点实验室开放研究课题(ZJ-KF-2023-1)。

摘　　要：采用高速剪切-高压均质法制备了具有不同含量ω-3多不饱和脂肪酸甘油酯的纳米乳并考察其在肝损伤治疗中的作用。通过单因素试验筛选出的优化工艺参数组合为:油相和水相以8000 r/min的剪切速度,在60℃下剪切5 min,然后以60000 kPa的均质压力循环6次。以优化工艺参数制备的纳米乳为白色均匀乳状液,平均粒径约为200 nm,pH值约为7.4,各项指标均符合质量要求。细胞摄取试验结果显示,所制备的纳米乳可以被人正常肝细胞(LO2细胞)有效摄取,且摄取量与ω-3多不饱和脂肪酸含量呈正相关。在胆汁淤积性肝损伤小鼠模型中,尾静脉注射纳米乳可有效改善小鼠肝损伤,且ω-3多不饱和脂肪酸甘油酯含量高的纳米乳对肝损伤小鼠的治疗作用较好。该研究制备的ω-3多不饱和脂肪酸甘油酯纳米乳可显著改善肝损伤,具有良好的临床应用潜力,可为注射型甘油酯纳米乳药物的优化设计提供有效参考。Several nanoemulsions with different contents ofω-3 polyunsaturated fatty acid glyceride were prepared by the high-speed shearing and high-pressure homogenization method and their effects on the treatment of liver injury were investigated.The combination of optimized process parameters selected through the experiment of single factor was as follows:the oil phase and the water phase were sheared at a shearing speed of 8000 r/min for 5 min at 60℃,and then homogenized at a pressure of 60000 kPa for 6 cycles.The nanoemulsion prepared with the optimized process parameters presented a white emulsion appearance,with an average particle size of approximately 200 nm and a pH value of approximately 7.4,and all indicators met the quality requirements.The results of the cell uptake test showed that the prepared nanoemulsions could be effectively taken up by human fetal hepatocyte cell line(LO2 cell),and the uptake amount was positively correlated with theω-3 polyunsaturated fatty acid content.As for the cholestatic liver injury model mouse,tail vein injection of nanoemulsions could effectively improve liver injury,and the nanoemulsions with a highω-3 polyunsaturated fatty acid glyceride content showed a better therapeutic effect on liver-injured mice.In conclusion,theω-3 polyunsaturated fatty acid glyceride nanoemulsions prepared in this study had a significant improvement effect on liver injury and good clinical application potential,providing an effective reference for the optimal design of injectable glyceride nanoemulsion drugs.

关 键 词：Ω-3多不饱和脂肪酸 甘油酯 纳米乳 质量评价 肝损伤 

分 类 号：R575[医药卫生—消化系统] R944.9[医药卫生—内科学]