目的 考察甘草次酸衍生物介导的香豆素6(Cou6)脂质体的物理稳定性,确定不同稳定性评价方法对脂质体的适用性。方法 采用薄膜分散-超声法制备Cou6普通脂质体、PEG修饰脂质体、甘草次酸衍生物介导的脂质体,分别考察6种脂质体的稳定常数、膜稳定性、血清稳定性和泄漏率。结果 未经修饰的脂质体物理稳定性较差,甘草次酸衍生物介导的脂质体,15 min的稳定常数为5.37~7.32;半数脂质体膜被破坏,Triton X-100的浓度为0.207‰~0.380‰;在24 h内血清稳定性变化不大,可以较好地抵抗血清的影响;7与14 d泄漏率以及泄漏率增加量均较小。结论 物理稳定性是脂质体重要的制剂学性质,所采用的稳定常数、血清稳定性和泄漏率研究方法以及所建立的膜稳定性测定方法能够对甘草次酸衍生物介导的脂质体物理稳定性进行评价。
Abstract
OBJECTIVE To evaluate the physical stability of glycyrrhetinic acid derivatives-mediated coumarin 6(Cou6) liposomes and confirm the applicability of different stability tests on liposomes. METHODS Film dispersion-ultrasonic method was used to prepare Cou6 liposomes, PEG-modified liposomes and glycyrrhetinic acid-mediated liposomes. The stability constants, membrane stability, serum stability and leakages of the six kinds of liposomes were studied. RESULTS The physical stability of the liposomes without modification was poor. As for the glycyrrhetinic acid-mediated liposomes, the stability constants at 15 min were 5.37-7.32 and the concentrations of Triton X-100 were 0.207‰-0.380‰ when half liposome membranes were destroyed. The serum stability in 24 h and leakages in 7 or 14 d showed good stability with little change. CONCLUSION The physical stability is one of the key pharmaceutical properties of liposomes. The stability constant, serum stability and leakage tests and the method of membrane stability we have established can be used to study the stability of liposomes.
关键词
甘草次酸 /
脂质体 /
膜稳定性 /
物理稳定性
{{custom_keyword}} /
Key words
glycyrrhetinic acid /
liposome /
membrane stability /
physical stability
{{custom_keyword}} /
中图分类号：
R944
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] HUANG Z, SUN Y, HU H, et al. Techniques and methods evaluation on pharmaceuticalstability of liposomes[J]. Acta Pharm Sin(药学学报),2016, 51(3):356-361.
[2] NEGISHI M, IRIE A, NAGATA N, et al. Specific binding of glycyrrhetinic acid to the rat liver membrane[J]. Biomembranes, 1991,1066(1):77-82.
[3] CAI Y, XU Y, CHAN HF, et al. Glycyrrhetinic acid mediated drug delivery carriers for hepatocellular carcinoma therapy[J]. Mol Pharm, 2016,13 (3):699-709.
[4] AKBARZADEH A, REZAEI-SADABADY R, DAVARAN S, et al. Liposome:classification, preparation, and applications[J]. Nanoscale Res Lett, 2013, 8(1):102.
[5] LANGERD, CZARCZYNSKAGOSLINSKA B, GOSLINSKI T. Glycyrrhetinic acid and its derivatives in infectious diseases[J]. Curr Issu Pharm Med Sci,2016,29 (3):118-123.
[6] WANG W, ZHANG N, SHAN W, et al. Preparation and characterization of TPGS-modified doxorubicin liposomes[J]. Chin Pharm J(中国药学杂志),2011,46(17):1340-1344.
[7] NIU G, PAN H, ZHANG J, et al. Preparation of methoxy-poly(ethylene glycol)-phosphatidylethanolamineand its stabilizing effect on liposomes[J]. Chin J Phram(中国医药工业杂志),2003,34(10):501-503.
[8] TAN C, XIA S, XUE J, et al. Liposomes as vehicles for lutein:preparation, stability, liposomal membrane dynamics, and structure[J]. J Agric Food Chem, 2013, 61(34):8175-8184.
[9] MATSUURA M, YAMAZAKI Y, SUGIYAMA M, et al. Polycation liposome-mediated gene transfer in vivo[J]. BBA,2003, 1612(2):136-143.
[10] CHERTOK B, DAVID A E, MOFFAT B A, et al. Substantiating in vivo magnetic brain tumor targeting of cationic iron oxide nanocarriers via adsorptive surface masking[J]. Biomaterials,2009,30(35):6780-6787.
[11] SAW P E, PARK J, LEE E, et al. Effect of PEG pairing on the efficiency of cancer-targeting liposomes[J]. Theranostics, 2015,5(7):746-754.
[12] MAO S, HOU S, JIN H, et al. Preparation of liposomes surface-modifiedwith glycyrrhetinic acid targeting to hepatocytes[J]. China J Chin Mater Med(中国中药杂志), 2003,28(10):328-331.
[13] CADDEO C, PUCCI L, GABRIELE M, et al. Stability, biocompatibility and antioxidant activity of PEG-modifiedliposomes containing resveratrol[J]. Int J Pharm,2018,538 (1):40-47.
[14] LOPEZ O, DE LA MAZA A, CODERCH L, et al. Direct formation of mixed micelles in the solubilization of phospholipid liposomes by Triton X-100[J]. FEBS Lett, 1998,426(3):314-318.
[15] YANG Y, XIE X, YANG Y, et al. A review on the influences of size and surface charge of liposome on its targeted drug delivery in vivo[J]. Acta Pharm Sin(药学学报), 2013,48(11):1644-1650.
[16] SHAI W, ZHANG X, CHEN J, et al. Preparation and characterization of chitosan-modified liposomes[J]. Chin Pharm J(中国药学杂志),2007, 42(15):1159-1163.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
辽宁省自然科学基金项目资助(201602312)
{{custom_fund}}
PDF(1666 KB)
