表面活性剂-醇质体增强多烯紫杉醇经皮给药的渗透性研究

doi:10.5246/jcps.2011.05.059

表面活性剂-醇质体增强多烯紫杉醇经皮给药的渗透性研究

邱玉琴, 李爽, 李芳, 张锁慧, 高云华^*

1. 中国科学院理化技术研究所光化学转换与功能材料重点实验室, 北京 100190
2. 中国科学院研究生院, 北京 100049

收稿日期:2010-12-24 修回日期:2011-05-10 出版日期:2011-09-20 发布日期:2011-09-20
通讯作者: 高云华*

Enhancement of transdermal delivery of docetaxel by surfactant-ethanolic liposomes

Yu-Qin Qiu, Shuang Li, Fang Li, Suo-Hui Zhang, Yun-Hua Gao^*

1. Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China
2. Graduate University of Chinese Academy of Sciences, Beijing 100049, China

Received:2010-12-24 Revised:2011-05-10 Online:2011-09-20 Published:2011-09-20
Contact: Yun-Hua Gao*

摘要/Abstract

摘要：

皮肤的屏障作用使大部分药物无法实现透皮给药。本文以改善难溶性大分子模型药物多烯紫杉醇 (docetaxel, DTX) 的经皮渗透性为主体思路, 研制了DTX的表面活性剂-醇质体 (surfactant-ethanlic liposomes, SEL)。SEL由磷脂、乙醇、胆酸钠、DTX和磷酸盐缓冲液组成, 采用薄膜分散法制备。对SEL的囊泡形态 (冷冻蚀刻电镜法)、粒径大小及分布进行了表征, 并测定包封率和载药量。采用体外扩散池实验研究了DTX表面活性剂-醇质体的经皮渗透性。结果表明, 当磷脂与表面活性剂的比例为85:15时, DTX的稳态透皮速率和累计透皮量均为最高, 且优于表面活性剂脂质体、醇质体和普通脂质体。最优处方的粒径分布、形态和载药量均较为稳定。本研究表明, 通过将DTX包载于SEL中可显著改善DTX的经皮渗透性。

关键词: 表面活性剂-醇质体, 经皮给药, 多烯紫杉醇, 透皮实验

Abstract: One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present study, we developed a surfactant-ethanolic liposomal system to improve the transdermal delivery of docetaxel (DTX), a model drug for high molecular weight and poorly water-soluble drugs. Surfactant-ethanolic liposomes (SEL) were composed of phospholipids, ethanol, sodium cholate, DTX and PBS which were prepared by thin film dispersion method. The developed formulations were characterized by determining the vesicle shape and surface morphology, size and size distribution, entrapment efficiency and drug loading capacity. The effects of the developed formulations on the permeation of DTX across rat skin in vitro were investigated using the modified Franz diffusion cell under both occlusive and non-occlusive application conditions. The DTX SELs with optimum composition (phospholipid–surfactant, 85:15, w/w) provided a significantly higher steady-state amount of flux and cumulative permeation, compared to the tranditional liposomes, surfactant liposomes and ethanolic liposomes. The optimal SELs exhibited stable vesicle size, morphology and drug loading capacity. Our results indicated that SELs were promising carriers to enhance the transdermal delivery of DTX.

Key words: Surfactant-ethanolic liposomes, Transdermal delivery, Docetaxel, Permeation study

中图分类号:

R943.43

Supporting: Foundation item: The Key Direction Program of Chinese Academy of Sciences (Grant No. kjcx2-sw-h12-01).
^*Corresponding author. Tel./Fax: 86-10-82543581

邱玉琴, 李爽, 李芳, 张锁慧, 高云华^*. 表面活性剂-醇质体增强多烯紫杉醇经皮给药的渗透性研究[J]. , DOI: 10.5246/jcps.2011.05.059.

Yu-Qin Qiu, Shuang Li, Fang Li, Suo-Hui Zhang, Yun-Hua Gao^*

. Enhancement of transdermal delivery of docetaxel by surfactant-ethanolic liposomes[J]. , DOI: 10.5246/jcps.2011.05.059.

参考文献

[1] Guy, R.H.; Hadgraft, J. Transdermal drug delivery, in Drugs and the Pharmaceutical Sciences (Swarbrick, J. Ed.), Vol 123. New York: Marcel Dekker. 2003, 1-23.
[2] Bos, J.D.; Meinardi, M.M.H.M. Exp. Dermatol. 2000, 9, 165-169.
[3] Barry, B.W. Eur. J. Pharm. Sci. 2001, 14, 101-114.
[4] Elsayed, M.M.A.; Abdallah, O.Y.; Naggar, V.F.; Khalafallah, N.M. Int. J. Pharm. 2007, 332, 1-16.
[5] Touitou, E.; Dayan, N.; Bergelson, L.; Godin, B.; Eliaz, M. J. Control. Release. 2000, 65, 403-418.
[6] Suwakul, W.; Ongpipattanakul, B.; Vardhanabhuti, N. J. Liposome Res. 2006, 16, 391-401.
[7] Cevc, G.; Blume, G. Biochim. Biophys. Acta. 1992, 1104, 226-232.
[8] Cevc, G.; Schatzlein, A.; Blume, G. J. Control. Release. 1995, 36, 3-16.
[9] Cevc, G.; Blume, G.; Schatzlein, A. J. Control. Release. 1997, 45, 211-226.
[10] Dayan, N.; Touitou, E. Biomaterials. 2000, 21, 1879-1885.
[11] Bendas, E.R.; Tadros, M.I. AAPS PharmSciTech. 2007, 8, E1-E8.
[12] Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council, Guide for the Care and Use of Laboratory Animals (National Academy Press, Washington, D.C. 1996).
[13] Panchagnula, R.; Desu, H.; Jain, A.; Khandavilli, S. J. Pharm. Sci. 2004, 93, 2177-2183.
[14] Trotta, M.; Peira, E.; Debernardi, F.; Gallarate, M. Int. J. Pharm. 2002, 241, 319-327.
[15] Cevc, G. Adv. Drug Deliv. Rev. 2004, 56, 675-711.
[16] El Maghraby, G.M.M.; Williams, A.C.; Barry, B.W. Int. J. Pharm. 2000, 196, 63-74.
[17] Kirjavainen, M.; Urtti, A.; Jaaskelainen, I.; Suhonen, T.M.; Paronen, P.; Koskela, R.V.; Kiesvaara, J.; Monkkonen, J. Biochim. Biophys. Acta. 1996, 1304, 179-189.
[18] Williams, A.C.; Barry, B.W. Adv. Drug Deliv. Rev. 2004, 56, 603-618.
[19] Immordino, M.L.; Brusa, P.; Arpicco, S.; Stella, B.; Dosio, F.; Cattel, L. J. Control. Release. 2003, 91, 417-429.