胰岛素经电致孔透皮传输过程中在皮肤中的滞留
摘 要:目的研究和克服胰岛素在电致孔下经皮传输过程中在皮肤中的滞留,提高胰岛素的经皮渗透速率.方法体外实验,裸鼠皮肤.采用荧光标记的手段研究胰岛素在皮肤中的滞留情况,使用表面活性剂十六烷基三甲基溴化铵(CTAB)阻止胰岛素的聚集,减少药物在皮肤中的滞留.结果超过50%的胰岛素在电致孔经皮传输的过程中滞留于皮肤中,滞留量随脉冲时间常数的减小和胰岛素浓度的增加而增加;滞留胰岛素在再次进行脉冲时可部分的释放,但是活性明显下降.在供给液中加入CTAB,其与胰岛素的物质的量之比为15时,胰岛素滞留减小20%,电致孔时的经皮渗透速率提高1倍多.结论胰岛素在皮肤中的积累是限制其在电致孔下经皮传输速率的主要原因之一,通过阻止分子聚集和疏通LTRs的方法可以减小药物的滞留,提高经皮传输速率.
关键词:胰岛素;经皮给药;电致孔;十六烷基三甲基溴化铵
分类号:Q518.4;R965.1 文献标识码:A
文章编号:1001-2494(2005)07-0525-04
关键词:胰岛素;经皮给药;电致孔;十六烷基三甲基溴化铵
分类号:Q518.4;R965.1 文献标识码:A
文章编号:1001-2494(2005)07-0525-04
基金项目:国家自然科学基金(20376038);教育部高校博士点基金(20020003056)
作者简介:蒋国强,男,博士研究生,通讯作者:丁富新,男,教授,博士生导师Tel:(010)62785534 Fax:(010)62770304 E-mail:Dingfx@tsinghua.edu.cn
作者单位:蒋国强(清华大学化工系,北京,100084)
朱德权(清华大学化工系,北京,100084)
昝佳(清华大学化工系,北京,100084)
戚明(清华大学化工系,北京,100084)
丁富新(清华大学化工系,北京,100084)
作者简介:蒋国强,男,博士研究生,通讯作者:丁富新,男,教授,博士生导师Tel:(010)62785534 Fax:(010)62770304 E-mail:Dingfx@tsinghua.edu.cn
作者单位:蒋国强(清华大学化工系,北京,100084)
朱德权(清华大学化工系,北京,100084)
昝佳(清华大学化工系,北京,100084)
戚明(清华大学化工系,北京,100084)
丁富新(清华大学化工系,北京,100084)
参考文献:
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[2]Zewert TE, Pliquett UF, Langer R, et al. Creation of transdermal pathways for macromolecule transport by skin electroporation and low toxicity, pathway-enlarging molecule [ J ]. Bioelectrochem Bioenerg,1999,49:11.
[3]Zewert TE, Pliquett F, Langer R, et al. Transport of DNA antisence oligonucleotide across human skin by electroporation [ J]. Biophys Res Commun, 1995,212: 286.
[4]蒋国强,昝佳,戚明,等.胰岛素经皮给药研究的新进展[J].精细化工,2003,20:412
[5]Sen A, Daly ME, Hui SW. Transdermal insulin delivery using lipid enhanced electroporation[ J]. Biomed Biochim Acta ,2002, 1564: 5.
[6]潘妍,赵会英,郑俊民.电致孔和离子导入对胰岛素经皮渗透的促进作用[J].药学学报,2002,37:649.
[7]张烜,张强,齐宪荣.HPLC法测定胰岛素脂质体中胰岛素的含量[J].中国现代应用药学杂志,2001,18(6):451.
[8]Fisher BV, Smith D. HPLC as a replacement for the animal response assays for insulin [ J ]. J Pharmaceut Biomed , 1986,4: 377.
[9]Pliquett UF, Vanbever R, Preat V, et al. Lacal transport regions (LTRs) in human stratum corneum due to long and short-high voltage' pulses [ J ]. Bioelectrochem Bioenerg, 1998,47:151.
[10]Chawla AS, Hinberg I, Blais P, et al. Aggregation of insulin, containing surfactant, in contact with different materials [J]. Diabetes,1985,34:420.
[11]Shao Z, Li YP, Krishnamoorthy R, et al. Differential effects of anionic, cationic, nonionic and physiologic surfactant on the dissociation, a-chymotryptic degradation, and enteral absorption of insulin hexamers[J]. Pharm Res,1993, 10: 243.
收稿日期:2004年7月13日
出版日期:2005年4月8日