食品科学 ›› 2022, Vol. 43 ›› Issue (16): 9-18.doi: 10.7506/spkx1002-6630-20210901-006

• 食品化学 • 上一篇    下一篇

光甘草定/环糊精固体包合物的制备和性质

姚培培,樊金玲,李德锋,张晓宇,任国艳,杜琳   

  1. (河南科技大学食品与生物工程学院,河南 洛阳 471023)
  • 出版日期:2022-08-25 发布日期:2022-08-31
  • 基金资助:
    国家自然科学基金面上项目(31571800)

Preparation and Characterization of Glabridin/Cyclodextrin Solid Inclusion Complex

YAO Peipei, FAN Jinling, LI Defeng, ZHANG Xiaoyu, REN Guoyan, DU Lin   

  1. (College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China)
  • Online:2022-08-25 Published:2022-08-31

摘要: 采用分子对接和相溶解度结合的方法研究不同环糊精(cyclodextrin,CD)与光甘草定(glabridin,GLD)之间的包合能力,筛选出适宜包合GLD的CD;制备GLD/CD固体包合物,考察不同干燥方法、不同投料比对固体包合物的包合率、载药量和溶解度的影响;通过扫描电子显微镜、差示扫描量热法、傅里叶变换红外光谱法和分子对接技术分别对包合物的形貌、包合物中GLD的存在形式、GLD与CD的相互作用和空间构象进行研究;采用体外溶出实验考察GLD在包合前后溶出特性的变化;采用噻唑蓝法比较GLD及其包合物对人肝癌细胞株(HepG-2)细胞增殖的抑制作用。结果表明:多种CD都能与GLD形成物质的量比1∶1的包合物,其中2-磺丁基-β-环糊精(2-sulfobutyl-β-cyclodextrins,2-SBE-β-CD)包合GLD的能力优于其他CD及其衍生物;不同制备方法制备的GLD/2-SBE-β-CD固体包合物的包合率和载药量均无显著差异,但包合物的水溶性有一定差异。适当提高GLD与2-SBE-β-CD物质的量比,包合率虽有一定程度下降,但可显著提高载药量。GLD与2-SBE-β-CD物质的量比为1.5∶1时,冷冻干燥法制备的GLD/2-SBE-β-CD固体包合物的包合率和载药量分别为86.09%和22.39%。GLD与2-SBE-β-CD物质的量比为1∶1时,冷冻干燥法、喷雾干燥法、捏合法制得的包合物的饱和溶解度均大于83 mg/mL。不同制备方法得到的GLD/2-SBE-β-CD包合物形貌差异显著,但GLD在GLD/2-SBE-β-CD包合物中均以无定形非晶体结构存在。不同制备方法得到的GLD/2-SBE-β-CD包合物的溶出特性无显著差异;GLD/2-SBE-β-CD包合物在胃、肠液中的累积溶出率显著高于GLD及GLD/2-SBE-β-CD物理混合物;与GLD/H2O组相比,GLD/2-SBE-β-CD包合物对HepG-2细胞的抗增殖活性有显著提高;本研究结果证实了2-SBE-β-CD作为GLD载体的优越性,有望拓宽GLD在食品、保健品等领域的应用。

关键词: 光甘草定;环糊精;固体包合物;制备;优化;表征;溶出;抗细胞增殖活性

Abstract: In order to select a suitable cyclodextrin (CD) for the inclusion complexation of glabridin (GLD), the inclusion capacity of different CDs for GLD was studied by molecular docking and phase solubility method. The effects of different drying methods and GLD/CD ratios on the inclusion rate, drug loading and solubility of solid inclusion complexes were investigated. The morphology of inclusion complexes, the existing form of GLD in inclusion complexes, the interaction between GLD and CD and the spatial conformation of inclusion complexes were investigated by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy and molecular docking, respectively. The dissolution properties of GLD before and after inclusion complexation were investigated by in vitro dissolution experiments. Methylthiazolyl tetrazolium (MTT) assay was used to compare the inhibitory effect of GLD and its inclusion complexes on the proliferation of human hepatoma cell line (HepG-2). The results showed that various CDs could form 1:1 inclusion complexes with GLD, and 2-sulfobutyl-β-CD (2-SBE-β-CD) had a better capability to include GLD than other CDs and their derivatives. There was no significant difference in the inclusion rate or drug loading of GLD/2-SBE-β-CD solid inclusion complexes prepared by different preparation methods, but the water solubility of the inclusion complexes was different. Appropriately increasing the ratio of GLD to 2-SBE-β-CD reduced the inclusion rate to a certain extent but significantly increased the drug loading. The inclusion rate and drug loading of the GLD/2-SBE-β-CD solid inclusion complex prepared with a 1.5:1 molar ratio between GLD and 2-SBE-β-CD by freeze-drying method were 86.09% and 22.39%, respectively. The saturated solubility of the inclusion compounds prepared with a 1:1 molar ratio between GLD and 2-SBE-β-CD by freeze-drying, spray-drying and kneading were all greater than 83 mg/mL. These inclusion complexes had significantly different morphology, but GLD existed in an amorphous structure in all of them. However, there was no significant difference in the dissolution properties of the inclusion complexes. The cumulative dissolution rates of the GLD/2-SBE-β-CD inclusion complexes in gastric and intestinal fluid were significantly higher than that of GLD and its physical mixture with 2-SBE-β-CD. The GLD/2-SBE-β-CD inclusion complexes had significantly enhanced anti-proliferative activity on HepG-2 cells compared with GLD/H2O. The results of this study confirm that the superiority of 2-SBE-β-CD as a GLD carrier is expected to broaden the application of GLD in food, health products and other fields.

Key words: glabridin; cyclodextrin; solid inclusion complex; preparation; optimization; characterization; dissolution; anti-cell proliferation activity

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