药学学报, 2021, 56(11): 3159-3165
引用本文:
龙家英, 李小芳*, 王娴, 邓茂, 古环, 谢龙, 陈慧娟, 代小琳. 茶皂素用于稳定橙皮苷纳米混悬剂及其机制研究[J]. 药学学报, 2021, 56(11): 3159-3165.
LONG Jia-ying, LI Xiao-fang*, WANG Xian, DENG Mao, GU Huan, XIE Long, CHEN Hui-juan, DAI Xiao-lin. Tea saponin stabilizing hesperidin nanosuspensions and its mechanism[J]. Acta Pharmaceutica Sinica, 2021, 56(11): 3159-3165.

茶皂素用于稳定橙皮苷纳米混悬剂及其机制研究
龙家英, 李小芳*, 王娴, 邓茂, 古环, 谢龙, 陈慧娟, 代小琳
成都中医药大学药学院, 中药材标准化教育部重点实验室, 西南特色中药资源国家重点实验室, 四川 成都 611137
摘要:
以茶皂素 (tea saponin,TS) 为稳定剂,制备橙皮苷纳米混悬剂 (hesperidin nanosuspensions,HDN-NS),考察TS作为新型天然稳定剂的可行性及其稳定纳米混悬剂的机制,为橙皮苷绿色纳米制剂的开发提供参考。以高速剪切联合高压均质法制备HDN-NS,以平均粒径及多分散指数为评价指标,采用单因素实验考察药物浓度、剪切速度、剪切时间、均质压力和均质次数对HDN-NS的影响。单因素实验考察结果为: 药物浓度为8.0 mg·mL-1,剪切转速为16 000 r·min-1,剪切时间为2 min,在35 MPa下均质6次,再在100 MPa下均质12次。通过pH、离子强度、zeta电位和TS的临界胶束浓度等因素考察,确定静电斥力在TS稳定纳米混悬剂的机制中发挥的作用。稳定机制考察结果说明,静电斥力参与了TS稳定HDN-NS的机制。由此可知,低浓度下的TS可显著降低HDN-NS的粒径,表明TS具有稳定纳米混悬剂的潜力,静电作用是TS稳定纳米混悬剂的机制之一。
关键词:    茶皂素      橙皮苷      纳米混悬剂      制备工艺      稳定机制      绿色纳米制剂      天然稳定剂     
Tea saponin stabilizing hesperidin nanosuspensions and its mechanism
LONG Jia-ying, LI Xiao-fang*, WANG Xian, DENG Mao, GU Huan, XIE Long, CHEN Hui-juan, DAI Xiao-lin
The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Abstract:
Hesperidin nanosuspensions (HDN-NS) were prepared with tea saponin (TS) as stabilizer. The feasibility of TS as a natural stabilizer and the mechanism of TS stabilized nanosuspensions were investigated to provide reference for the development of green nano-preparations of hesperidin. HDN-NS was prepared by high-speed shearing combined with high-pressure homogenization. Using average particle size and polydispersity index as evaluation indexes, the effects of drug concentration, shearing speed, shearing time, homogeneous pressure and homogeneous cycles on HDN-NS were investigated by single factor experiment. The results of single factor investigation were as follows: drug concentration was 8.0 mg·mL-1, shearing speed was 16 000 r·min-1, shearing time was 2 min, the homogeneous cycles were 6 cycles at 35 MPa and 12 cycles at 100 MPa. The pH, ionic strength, zeta potential and critical micelle concentration of TS were investigated to determine the role of electrostatic repulsion in the mechanism of TS stabilized nanosuspensions. The results showed that electrostatic repulsion is involved in the mechanism of TS stabilized HDN-NS. In conclusion, at low concentration, TS can significantly reduce the particle size of HDN-NS, which indicates that TS has the potential to stabilize nanosuspension. Electrostatic repulsion is one of the mechanisms of TS stabilizing nanosuspension.
Key words:    tea saponin    hesperidin    nanosuspension    preparation technology    stabilizing mechanism    green nano-preparation    natural stabilizer   
收稿日期: 2021-04-08
DOI: 10.16438/j.0513-4870.2021-0551
基金项目: 四川省科技创新苗子工程项目(2020095);四川省科技厅重点项目(2019YFS0113).
通讯作者: 李小芳,Tel:13808195110,E-mail:lixiaofang@cdutcm.edu.cn
Email: lixiaofang@cdutcm.edu.cn
相关功能
PDF(1736KB) Free
打印本文
0
作者相关文章
龙家英  在本刊中的所有文章
李小芳*  在本刊中的所有文章
王娴  在本刊中的所有文章
邓茂  在本刊中的所有文章
古环  在本刊中的所有文章
谢龙  在本刊中的所有文章
陈慧娟  在本刊中的所有文章
代小琳  在本刊中的所有文章

参考文献:
[1] Guazelli CFS, Fattori V, Ferraz CR, et al. Antioxidant and anti-inflammatory effects of hesperidin methyl chalcone in experimental ulcerative colitis[J]. Chem Biol Interact, 2021, 333: 109315.
[2] Wunpathe C, Potue P, Maneesai P, et al. Hesperidin suppresses renin-angiotensin system mediated NOX2 over-expression and sympathoexcitation in 2K-1C hypertensive rats[J]. Am J Chin Med, 2018, 46: 751-767.
[3] Welbat JU, Naewla S, Pannangrong W, et al. Neuroprotective effects of hesperidin against methotrexate-induced changes in neurogenesis and oxidative stress in the adult rat[J]. Biochem Pharmacol, 2020, 178: 114083.
[4] Kongtawelert P, Wudtiwai B, Shwe TH, et al. Inhibitory effect of hesperidin on the expression of programmed death ligand (PD-L1) in breast cancer[J]. Molecules, 2020, 25: 252.
[5] Zheng DY, Deng YT, Xia Y, et al. Fabrication and performance of a spherical cellulose nanocrystal-based hydrophobic drug delivery vehicle using rubber wood[J]. Bioresources, 2019, 14: 7763-7774.
[6] Ji YB, Liu B, Yu RQ, et al. Preparation of disulfiram naonosuspensions and their anti-tumor efficacy in vitro and in vivo[J]. Acta Pharm Sin (药学学报), 2019, 54: 565-573.
[7] Wang JL, Yao JH, Ning Q, et al. Beneficial effects of nanosuspensions of honokiol in mice on high fat diet through suppression of hepatic gluconeogenesis[J]. Acta Pharm Sin (药学学报), 2019, 54: 288-293.
[8] Kansom T, Sajomsang W, Saeeng R, et al. Fabrication and characterization of andrographolide analogue (3A.1) nanosuspensions stabilized by amphiphilic chitosan derivatives for colorectal cancer therapy[J]. J Drug Deliv Sci Technol, 2019, 54: 101287.
[9] Heydenreich AV, Westmeier R, Pedersen N, et al. Preparation and purification of cationic solid lipid nanospheres--effects on particle size, physical stability and cell toxicity[J]. Int J Pharm, 2003, 254: 83-87.
[10] Hawkins MJ, Soon-Shiong P, Desai N. Protein nanoparticles as drug carriers in clinical medicine[J]. Adv Drug Deliv Rev, 2008, 60: 876-885.
[11] Muller RH, Keck CM. Challenges and solutions for the delivery of biotech drugs--a review of drug nanocrystal technology and lipid nanoparticles[J]. J Biotechnol, 2004, 113: 151-170.
[12] Xuan JJ, Wu XY, Qi JP, et al. Application of natural deep eutectic solvents in pharmaceutics[J]. Acta Pharm Sin (药学学报), 2021, 56: 146-157.
[13] Chen Y, Liu Y, Xu J, et al. A natural triterpenoid saponin as multifunctional stabilizer for drug nanosuspension powder[J]. AAPS PharmSciTech, 2017, 18: 2744-2753.
[14] Ma Y, Gao Y, Zhao X, et al. A natural triterpene saponin-based Pickering emulsion[J]. Chem A Eur J, 2018, 24: 11703-11710.
[15] Xie Y, Ma Y, Xu J, et al. Panax notoginseng saponins as a novel nature stabilizer for poorly soluble drug nanocrystals: a case study with baicalein[J]. Molecules, 2016, 21: 1149.
[16] Golemanov K, Tcholakova S, Denkov N, et al. Remarkably high surface visco-elasticity of adsorption layers of triterpenoid saponins[J]. Soft Matter, 2013, 9: 5738-5752.
[17] Wan ZL, Sun YG, Ma LL, et al. Responsive emulsion gels with tunable properties formed by self-assembled nanofibrils of natural saponin glycyrrhizic acid for oil structuring[J]. J Agric Food Chem, 2017, 65: 2394-2405.
[18] Cai JR, Lv JJ. Research progress of natural surfactant tea saponin[J]. China Clean Ind (中国洗涤用品工业), 2018, (12): 83-88.
[19] Zhu Z, Wen Y, Yi J, et al. Comparison of natural and synthetic surfactants at forming and stabilizing nanoemulsions: tea saponin, Quillaja saponin, and Tween 80[J]. J Colloid Interface Sci, 2019, 536: 80-87.
[20] Liu LN, Li XF, Zhong L, et al. Preparation of baicalin solid nanocrystal using glycyrrhizic acid as a natural stabilizer[J]. Chin Tradit Herbal Drugs (中草药), 2019, 50: 2057-2064.
[21] Yuan HL, Yi JM, Zhang CY, et al. Progress in research of preparation technologies and drug-delivery of nanosuspensions[J]. Chin J New Drug (中国新药杂志), 2014, 23: 297-301.
[22] Zhang J. Studies on TFu-loaded Nanosuspensions (托氟啶纳米混悬剂的研究)[D]. Jinan: Shandong University, 2012.
[23] Xu Q, Huang QQ, Wang YL, et al. Progress in physical stability of nanosuspensions[J]. Chin J Pharm (中国医药工业杂志), 2012, 43: 148-152.
[24] Guan J, Zhang Y, Liu Q, et al. Exploration of alginates as potential stabilizers of nanosuspension[J]. AAPS PharmSciTech, 2017, 18: 3172-3181.
[25] Tang HL, Li XF, Long JY, et al. Preparation of silymarin nanosuspension with glycyrrhizic acid as stabilizer and study of its stabilization mechanism[J]. Chin Tradit Herb Drugs (中草药), 2020, 51: 971-977.
[26] Jian HL, Liao XX, Zhu LW, et al. Synergism and foaming properties in binary mixtures of a biosurfactant derived from Camellia oleifera Abel and synthetic surfactants[J]. J Colloid Interface Sci, 2011, 359: 487-492.
[27] Huang P, Mao KJ, Wang XT, et al. Research progress on stabilizers nanosuspensions[J]. Guangzhou Chem Ind (广州化工), 2016, 44: 7-9, 32.
[28] Long J, Song J, Zhang X, et al. Tea saponins as natural stabilizers for the production of hesperidin nanosuspensions[J]. Int J Pharm, 2020, 583: 119406.
[29] Uluata S, McClements DJ, Decker EA. Physical stability, autoxidation, and photosensitized oxidation of ω-3 oils in nanoemulsions prepared with natural and synthetic surfactants[J]. J Agric Food Chem, 2015, 63: 9333-9340.
[30] Böttcher S, Drusch S. Saponins - self-assembly and behavior at aqueous interfaces[J]. Adv Colloid Interface Sci, 2017, 243: 105-113.
[31] Liao Y, Zhong L, Liu L, et al. Comparison of surfactants at solubilizing, forming and stabilizing nanoemulsion of hesperidin[J]. J Food Eng, 2020, 281: 110000.