蛇床子素脂质体的制备及表征

doi:10.3969/j.issn.2095-1396.2017.05.004

神经药理学报

蛇床子素脂质体的制备及表征

赵凯燕，张丹参，苏晓梅，张海威，侯文书

1. 河北科技大学化学与制药工程学院，石家庄，050000，中国
2. 河北北方学院药学系，张家口，075000，中国

出版日期:2017-10-26 发布日期:2017-12-01
通讯作者: 张丹参，女，博士生导师；研究方向：神经药理学；E-mail：zhangds2011@126.com
作者简介:赵凯燕，女，硕士研究生；研究方向：神经药理学；E-mail：18132015769@163.com
基金资助:
河北省教育厅科学技术研究重点项目（No.ZD2016009）

Preparation and Characterization of Osthole Liposomes

ZHAO Kai-yan1，ZHANG Dan-shen1，SU Xiao-mei1，ZHANG Hai-wei2，HOU Wen-shu2

1.Hebei University of Science and Technology，College of Chemisty and Pharmaceutical Engineering，Shijiazhuang，050000，China
2. Hebei North University，Department of Pharmacology，Zhangjiakou，075000，China

Online:2017-10-26 Published:2017-12-01
Contact: 张丹参，女，博士生导师；研究方向：神经药理学；E-mail：zhangds2011@126.com
About author:赵凯燕，女，硕士研究生；研究方向：神经药理学；E-mail：18132015769@163.com
Supported by:
河北省教育厅科学技术研究重点项目（No.ZD2016009）

摘要/Abstract

摘要：

目的：对蛇床子素脂质体的制备方法、制备处方、制剂性质进行研究，并制备冻干脂质体提高制剂的稳定性。方法：以包封率和粒径分布为指标，筛选脂质体的制备方法；采用单因素方差分析和正交实验优化处方，测定优化后处方包封率、粒径、电位，观察电镜下形态；选择甘露醇为冻干保护剂，探究其加入量对冻干脂质体包封率的影响。结果：通过筛选选择乙醇注入法制备脂质体，制备温度为50℃，蛋黄卵磷脂（egg yolk lecithin，EPC）浓度为4 mg·mL-1，胆固醇（cholesterol，CHOL）加入量为5 mg，蛇床子素（osthole，Ost）加入量为2 mg为最优处方。脂质体包封率为（83.09±0.56）%，粒径为（101.9±2.7） nm，电位（-15.3±2.3） mV。当甘露醇加入量为8% 时，冻干脂质体形态较好、复溶后泄漏较少。结论：使用乙醇注入法制备得到的脂质体包封率高，粒径分布均匀，方法稳定，制备为冻干脂质体后，脂质体稳定性得到提高。

关键词: 蛇床子素, 脂质体, 乙醇注入法, 冻干脂质体

Abstract:

Objective：To research the preparation methods，prescriptions and preparation properties of osthole loaded liposomes，and the lyophilized liposomes was prepared to improve the stability of the preparation. Methods：Encapsulation efficiency was taken as index to screen the preparation of liposomes；the formulation was optimized by single factor prescription analysis and orthogonal test. The encapsulation efficiency，particle size and potential of the osthole
liposomes were measured，and the morphology under transmission electron microscope was observed；mannitol was selected as a freeze-drying agent，we explored the effect of its addition on the encapsulation efficiency of lyophilized liposomes. Results：The liposomes were prepared by ethanol injection method. The optimal formulations were EPC 4 mg·mL-1，CHOL 5 mg，Ost 2 mg，and at 50℃ reactive temperature. The encapsulation efficiency of liposome was （83.09±0.56） %，the particle size was（ 101.9±2.7） nm，and the potential was（ -15.3±2.3） mV. When the amount of mannitol was 8%，the lyophilized liposomes had better morphology and less leakage.Conclusion：Liposome which has high entrapment efficiency and well-distributed particle size was prepared by ethanol injection. After preparation of lyophilized liposomes，the stability of liposomes was improved.

Key words: osthole, liposome, ethanol injection, lyophilized liposomes

中图分类号:

R944.1

赵凯燕，张丹参，苏晓梅，张海威，侯文书. 蛇床子素脂质体的制备及表征[J]. 神经药理学报, DOI: 10.3969/j.issn.2095-1396.2017.05.004.

ZHAO Kai-yan1，ZHANG Dan-shen1，SU Xiao-mei1，ZHANG Hai-wei2，HOU Wen-shu2. Preparation and Characterization of Osthole Liposomes[J]. Acta Neuropharmacologica, DOI: 10.3969/j.issn.2095-1396.2017.05.004.

参考文献

[1] Hua Kuo-feng, Yang Shun-min, Kao Tzu-Yang, et al. Osthole mitigates progressive IgA nephropathy by inhibiting reactive oxygen species generation and NF-κB/NLRP3 pathway[J]. PLoS One, 2013, 8(10): e77794

[2] Liu Ya-wei Liu, Yung-Tsung Chiu, Fu Shu-ling, et al. Osthole ameliorates hepatic fibrosis and inhibits hepatic stellate cell activation[J]. Biomed Sci, 2015, 22(1): 63.

[3] Xu Xiao-man, Zhang Yi, Qu Dan, et al. Osthole induces G2/M arrest and apoptosis in lung modulating PI3K/Akt pathway[J]. Exp Clin Cancer Res, 2011, 30(1): 33.

[4] Luszczki Jarogniew J, AndresMach Marta, Cisowski Wojciech, et al. Osthole suppresses seizures in the mouse maximal electroshock seizure model[J]. Eur J Pharmacol, 2009, 607(1-3): 107-109.

[5] Leung Y M, Kuo Y H, Chao C C, et al. Osthol is a use dependent blocker of voltage-gated Na⁺ channels in mouseneuroblastoma N2A cells[J]. Planta Medica, 2010, 76(1): 34-40.

[6] Wu Sheng-nan, Lo Yuk-Kang Chen, Chien-Chich, et al. Inhibitory effect of the plant-extract Osthole on L-type calcium current in NG108-15 neuronal cells[J]. Biochemical Pharmacology, 2002, 63(2): 199-206.

[7] Liu Wen-bo, Zhou Jun, Qu Yan, et al. Neuroprotective effect of Osthole on MPP+-induced cytotoxicity in PC12 cells via inhibition of mitochondrial dysfunction and ROS production[J]. Neurochemistry International, 2010, 57(3): 206-215.

[8] 陆姗姗, 王冬月, 顾薇, 等. 转铁蛋白修饰香豆素-6脂质体的制备与评价[J]. 中国新药杂志, 2015, 24(13): 1537-1540

[9] 赖滢滢, 王岩, 张英丰. 星点设计-效应面法进行蛇床子素脂质体处方优化的研究[J]. 中国新药杂志, 2015, 24(06): 708-712+720.

[10] Catherine Charcosset, Audrey Juban, Jean-Pierre Valour, et al. Preparation of liposomes at large scale using the ethanol inj ection method: Effect of scale-up and inj ection devices[J]. Chemical Engineering Research and Design, 2015, 94(2): 508-515.

[11] 张成龙, 张季, 康聪, 等.蛇床子素脂质体的处方优化及其体外释放度[J]. 中国医药工业杂志, 2016, 47(06): 728-731.

[12] 赖滢滢. 蛇床子素脂质体凝胶的制备与评价[D]. 广州：广东药科大学, 2016.

[13] 赵凯燕, 张丹参. 脂质体包封率的研究进展[J]. 神经药理学报, 2016, 6(06): 23-30.

[14] Liu Yan, Luo Xiao, Xu Xiao-chao, et al. Preparation characterization and in vivo pharmacokinetic study of PVP-modified oleanolic acid liposomes[J]. Int J Pharm, 2017, 517 (1-2): 1-7.

[15] 唐文雅, 宋艳志, 邓意辉. 脂质体冻干保护剂的种类及其作用机制研究进展[J]. 沈阳药科大学学报, 2012, 29(07): 560-569.

蛇床子素脂质体的制备及表征

Preparation and Characterization of Osthole Liposomes

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