阿魏酸川芎嗪长循环固体脂质纳米粒的制备及体外巨噬细胞摄取研究

Preparation and Macrophage Uptake in vitro of Long Circulating Tetramethylpyrazine Ferulate Solid Lipid Nanoparticles

目的:研究阿魏酸川芎嗪长循环固体脂质纳米粒(PEG-FATM-SLN)的制备方法,并考察其体外释放及细胞摄取性能。方法:采用乳化超声分散法,以包封率及粒径为考察指标,通过正交试验优化处方及工艺。以小鼠腹腔巨噬细胞(MPM)为模型做体外细胞摄取试验。结果:制备PEG-FATM-SLN最优处方为阿魏酸川芎嗪10 mg,单硬脂酸甘油酯0.3 g,乙酸丁酯1.5 ml,蛋黄卵磷脂0.4 g,泊洛沙姆1 880.6 g,硬脂酸钠0.02 g,水20 ml,二硬脂酰基磷脂酰乙醇胺-聚乙二醇2000(DSPEPEG2000)0.02 g。制备的样品粒径为(107.1±1.1)nm,包封率为(53.3±3.0)%。体外释放试验和巨噬细胞摄取试验结果表明,该制剂具有明显的缓释性能和抗巨噬细胞吞噬作用。结论:本研究制备了粒径小,包封率高的阿魏酸川芎嗪长循环固体脂质纳米粒,为其新剂型的研究提供了理论依据和试验基础。

Objective： To study the preparation method of tetramethylpyrazine ferulate solid lipid nanoparticles surface-modified by PEG （PEG-FATM-SLN） and investigate the drug release and cell uptake in vitro. Methods： PEG-FATM-SLN was prepared by an e- mulsion ultrasound dispersing method. The formula of PEG-FATM-SLN was optimized by orthogonal design with entrapment efficacy and particle size as the indices. The mouse peritoneal macrophage （MPM） model was used to evaluate the uptake of PEG-FATM-SLN by cells in vitro. Results： The optimal formula was as follows： tetramethylpyrazine ferulate 10 mg, glycerol monostearate 0.3 g, butyl acetate 1.5 ml, lecithin O. 4 g, poloxamer 1 88 0.6 g, sodium stearate 0.02 g, water 20 ml and DSPE-PEG2000 0.02 g. The mean size of PEG-FATM-SLN was （107.1 ± 1.1 ） nm and the encapsulation efficiency was （53.3 ± 3.0） %. The release and macrophage uptake test in vitro exhibited sustained release and antiphagocytic uptake characteristics. Conclusion： The long circulating tetramethyl- pyrazine ferulate solid lipid nanoparticles are prepared successfully with small particle size and high encapsulation efficiency, which provides theoretical and experimental basis for the study on new dosage forms of tetramethylpyrazine ferulate.